Regulation of mitotic cell cycle (Homo sapiens)

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<?xml version="1.0" encoding="UTF-8"?> <Pathway xmlns="http://pathvisio.org/GPML/2013a" Name="Regulation of mitotic cell cycle" Organism="Homo sapiens"> <Comment Source="WikiPathways-description">Regulation of mitotic cell cycle currently covers APC/C-mediated degradation of cell cycle proteins. 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RelX="-1.0" RelY="0.0" /> <Point X="187.0" Y="1756.0" GraphRef="f8823" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174124" /> </Interaction> <Interaction GraphId="b1417"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="482.0" Y="807.0" GraphRef="a2204" RelX="0.7300000000000182" RelY="0.0" /> <Point X="515.0" Y="863.0" GraphRef="dfb83" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174174" /> </Interaction> <Interaction GraphId="b15df"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="851.0" Y="466.0" GraphRef="a7487" RelX="-1.1399999999999864" RelY="0.18000000000000682" /> <Point X="847.0" Y="407.0" GraphRef="f1665" RelX="0.9701492537313433" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174058" /> </Interaction> <Interaction GraphId="b1740"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="579.0" Y="1582.0" GraphRef="e3323" RelX="-1.0" RelY="0.0" /> <Point X="537.0" Y="1620.0" GraphRef="e659a" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-141429" /> </Interaction> <Interaction GraphId="b17fa"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="611.0" Y="1109.0" GraphRef="c7cc5" RelX="0.9805825242718447" RelY="0.0" /> <Point X="561.0" Y="951.0" GraphRef="bd602" RelX="-30.5" RelY="0.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174159" /> </Interaction> <Interaction GraphId="b29eb"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1431.0" Y="1256.0" GraphRef="c3263" RelX="0.0" RelY="1.0" /> <Point X="1399.0" Y="1284.0" GraphRef="b14d3" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174120" /> </Interaction> <Interaction GraphId="b399e"> <Comment Source="Reactome">Nek2A does not appear to be recruited to the APC/C by Cdc20 but rather binds directly to the APC/C in an interaction involving the NEK2A C-terminal methionine–arginine (MR) dipeptide tail (Hayes et al., 2006).</Comment> <BiopaxRef>f2d</BiopaxRef> <BiopaxRef>b53</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="849.0" Y="1532.0" /> <Point X="849.0" Y="1663.0" /> <Anchor Position="0.0" Shape="None" GraphId="e1e52" /> <Anchor Position="0.99" Shape="None" GraphId="a038b" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-179410" /> </Interaction> <Interaction GraphId="b3bca"> <Comment Source="Reactome">Cdk mediated phosphorylation of Emi1 is believed to promotes its phospho- Ser145-Ser149 dependent association with beta-TrCP.</Comment> <BiopaxRef>e2c</BiopaxRef> <BiopaxRef>a6f</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="659.0" Y="1104.0" /> <Point X="658.0" Y="1048.0" /> <Anchor Position="0.0" Shape="None" GraphId="c4665" /> <Anchor 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RelY="1.9600000000000364" /> <Point X="620.0" Y="1156.0" GraphRef="bec35" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174203" /> </Interaction> <Interaction GraphId="b54fd"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="779.0" Y="510.0" GraphRef="e82ea" RelX="-0.8899999999999864" RelY="0.009999999999990905" /> <Point X="500.0" Y="499.0" GraphRef="e6c62" RelX="1.0" RelY="-0.013333333333333334" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174139" /> </Interaction> <Interaction GraphId="b593b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="951.0" Y="376.0" GraphRef="c0f2d" RelX="0.9823008849557522" RelY="0.0" /> <Point X="1054.0" Y="364.0" GraphRef="c5ca1" RelX="278.5" RelY="17.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-188191" /> </Interaction> <Interaction GraphId="b6603"> <Comment Source="Reactome">Phosphorylation of the APC/C is believed to be required for its activation. While the identity of the essential phosphorylation sites and the kinase(s) responsible are not known with certainty, in vitro studies have shown that the Apc1 and the tetratricopeptide repeat (TPR) subunits Cdc27, Cdc16, Cdc23 and Apc7 are phosphorylated and that the Cdk1 and Plk1 kinases may play a role.</Comment> <BiopaxRef>c5f</BiopaxRef> <BiopaxRef>b94</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="289.0" Y="513.0" /> <Point X="393.0" Y="507.0" /> <Anchor Position="0.0" Shape="None" GraphId="e3a1b" /> <Anchor Position="0.99" Shape="None" GraphId="d13d5" /> <Anchor Position="0.5" Shape="None" GraphId="f98bd" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174119" /> </Interaction> <Interaction GraphId="b84cb"> <Comment Source="Reactome">Cyclin A is believed to be recognized by the APC/C:Cdc20 complex through its D-box sequence, which is 10-20 residues longer than the D-box of cyclin B (Geley et al., 2001).</Comment> <BiopaxRef>e05</BiopaxRef> <BiopaxRef>a11</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1021.0" Y="1547.0" /> <Point X="1092.0" Y="1545.0" /> <Anchor Position="0.0" Shape="None" GraphId="dfdfa" /> <Anchor Position="0.99" Shape="None" GraphId="f1961" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174171" /> </Interaction> <Interaction GraphId="b8547"> <Comment Source="Reactome">Cdh1 is multiubiquitinated by the APC/C:Cdh1 complex prior to degradation by the 26S proteasome.</Comment> <BiopaxRef>d6f</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1032.0" Y="560.0" /> <Point X="1032.0" Y="471.0" /> <Anchor Position="0.0" Shape="None" GraphId="bdffc" /> <Anchor Position="0.99" Shape="None" GraphId="f44ef" /> <Anchor Position="0.5" Shape="None" GraphId="dc6cf" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174057" /> </Interaction> <Interaction GraphId="b87cb"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="396.0" Y="1330.0" GraphRef="c48dc" RelX="-1.0" RelY="0.0" /> <Point X="393.0" Y="1330.0" GraphRef="e3e41" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174105" /> </Interaction> <Interaction GraphId="b8902"> <Comment Source="Reactome">Multiubiquitinated Emi1 is degraded by the 26S proteasome.</Comment> <BiopaxRef>ab0</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="458.0" Y="979.0" /> <Point X="561.0" Y="1175.0" /> <Anchor Position="0.0" Shape="None" GraphId="c9446" /> <Anchor Position="0.99" Shape="None" GraphId="ffdd4" /> <Anchor Position="0.5" Shape="None" GraphId="bbaba" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174203" /> </Interaction> <Interaction GraphId="b8aa7"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="885.0" Y="1503.0" GraphRef="cc80a" RelX="-0.006802721088435374" RelY="0.92" /> <Point X="849.0" Y="1532.0" GraphRef="e1e52" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-179410" /> </Interaction> <Interaction GraphId="b8ea5"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="219.0" Y="1355.0" GraphRef="baa90" RelX="0.3499999999999943" RelY="-1.4300000000000637" /> <Point X="231.0" Y="1352.0" GraphRef="ceaf6" RelX="0.0" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174070" /> </Interaction> <Interaction GraphId="b972b"> <Comment Source="Reactome">Emi1 is also believed to be phosphorylated by Cyclin B:Cdc2 on a CDK consensus site at Ser 182. While Plk1 mediated phosphorylation of Emi1 at the DSGxxS (ßTrCP recognition) motif is essential for Emi1 destruction in mitosis, Cdk phosphorylation has been shown to play an important regulatory role.</Comment> <BiopaxRef>a6f</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="405.0" Y="719.0" /> <Point X="461.0" Y="719.0" /> <Anchor Position="0.0" Shape="None" GraphId="fe517" /> <Anchor Position="0.99" Shape="None" GraphId="b3bdd" /> <Anchor Position="0.5" Shape="None" GraphId="a1bf9" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174122" /> </Interaction> <Interaction GraphId="b9f11"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="286.0" Y="501.0" GraphRef="f0935" RelX="1.0" RelY="0.0" /> <Point X="289.0" Y="513.0" GraphRef="e3a1b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174119" /> </Interaction> <Interaction GraphId="ba5cb"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="863.0" Y="1087.0" GraphRef="ff297" RelX="0.0" RelY="1.0" /> <Point X="863.0" Y="1090.0" GraphRef="ffa8b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174202" /> </Interaction> <Interaction GraphId="bab94"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="413.0" Y="1411.0" GraphRef="e6067" RelX="1.0" RelY="0.0" /> <Point X="462.0" Y="1386.0" GraphRef="c7b77" RelX="0.0" RelY="-2.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174195" /> </Interaction> <Interaction GraphId="bb46e"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="977.0" Y="510.0" GraphRef="beb00" RelX="1.0" RelY="0.0" /> <Point X="1032.0" Y="508.0" GraphRef="dc6cf" RelX="0.0" RelY="-7.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174057" /> </Interaction> <Interaction GraphId="bb937"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1350.0" Y="286.0" GraphRef="ad60c" RelX="-1.0" RelY="0.0" /> <Point X="1301.0" Y="283.0" GraphRef="dd090" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-9686980" /> </Interaction> <Interaction GraphId="bbd6c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="365.0" Y="610.0" GraphRef="ce5dc" RelX="-1.0" RelY="-0.030303030303030304" /> <Point X="347.0" Y="495.0" GraphRef="fafee" RelX="6.0" RelY="-1.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174132" /> </Interaction> <Interaction GraphId="bbe27"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1070.0" Y="605.0" GraphRef="ebcca" RelX="1.0" RelY="0.0" /> <Point X="1379.0" Y="532.0" GraphRef="d5032" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-9686969" /> </Interaction> <Interaction GraphId="bbe9a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="864.0" Y="1188.0" GraphRef="e4100" RelX="0.009999999999990905" RelY="0.9800000000000182" /> <Point X="865.0" Y="1240.0" GraphRef="e4634" RelX="-0.012345679012345678" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174202" /> </Interaction> <Interaction GraphId="bc2ff"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="410.0" Y="762.0" GraphRef="d700f" RelX="0.9856115107913669" RelY="-0.02702702702702703" /> <Point X="405.0" Y="719.0" GraphRef="fe517" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174122" /> </Interaction> <Interaction GraphId="bcabd"> <Comment Source="Reactome">At the beginning of this reaction, 3 molecules of 'ubiquitin', and 1 molecule of 'cell cycle proteins:phospho-APC/C:Cdh1 complex' are present. At the end of this reaction, 1 molecule of 'multiubiquitinated cell cycle protein:APC/C:Cdh1 complex' is present.&lt;br&gt;&lt;br&gt; This reaction takes place in the 'cytosol' and is mediated by the 'ubiquitin-protein ligase activity' of 'cell cycle proteins:phospho-APC/C:Cdh1 complex' (Rape et al.1996).&lt;br&gt;</Comment> <BiopaxRef>e00</BiopaxRef> <BiopaxRef>d9c</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="462.0" Y="1411.0" /> <Point X="462.0" Y="1365.0" /> <Anchor Position="0.0" Shape="None" GraphId="d2d0d" /> <Anchor Position="0.99" Shape="None" GraphId="c42e7" /> <Anchor Position="0.5" Shape="None" GraphId="c7b77" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174195" /> </Interaction> <Interaction GraphId="bd34e"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1333.0" Y="1473.0" GraphRef="ff07b" RelX="-1.0" RelY="0.0" /> <Point X="1282.0" Y="1408.0" GraphRef="d116b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174227" /> </Interaction> <Interaction GraphId="bebd8"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="500.0" Y="409.0" GraphRef="b2ad7" RelX="0.983739837398374" RelY="0.0" /> <Point X="553.0" Y="394.0" GraphRef="f686c" RelX="-1.5" RelY="0.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174079" /> </Interaction> <Interaction GraphId="bf982"> <Comment Source="Reactome">In addition to its association with Cdh1 in G1 phase, Emi1 further contributes the inactivation of the APC/C between G2 and prophase by associating with another APC/C activator, Cdc20.</Comment> <BiopaxRef>fd2</BiopaxRef> <BiopaxRef>d00</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="921.0" Y="767.0" /> <Point X="921.0" Y="828.0" /> <Anchor Position="0.0" Shape="None" GraphId="b34bf" /> <Anchor Position="0.99" Shape="None" GraphId="a9de6" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174235" /> </Interaction> <Interaction GraphId="bfede"> <Comment Source="Reactome">At the beginning of this reaction, 1 molecule of 'Cdc20:phospho-APC/C:Cyclin B:Cdc2 complex', and 3 molecules of 'ubiquitin' are present. At the end of this reaction, 1 molecule of 'multiubiquitinated Cyclin B:Cdc2:Cdc20:phospho-APC/C complex' is present.&lt;br&gt;&lt;br&gt; This reaction takes place in the 'cytosol' and is mediated by the 'ubiquitin-protein ligase activity' of 'Cdc20:Phospho-APC/C'.&lt;br&gt;</Comment> <BiopaxRef>a11</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1282.0" Y="1408.0" /> <Point X="1204.0" Y="1407.0" /> <Anchor Position="0.0" Shape="None" GraphId="d116b" /> <Anchor Position="0.99" Shape="None" GraphId="b2cd2" /> <Anchor Position="0.5" Shape="None" GraphId="fbbbe" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174227" /> </Interaction> <Interaction GraphId="c020f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="709.0" Y="1499.0" GraphRef="df917" RelX="0.9858156028368794" RelY="-0.018867924528301886" /> <Point X="731.0" Y="1494.0" GraphRef="becad" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-141423" /> </Interaction> <Interaction GraphId="c066b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="231.0" Y="1352.0" GraphRef="ceaf6" RelX="0.0" RelY="1.0" /> <Point X="268.0" Y="1409.0" GraphRef="febe3" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174088" /> </Interaction> <Interaction GraphId="c1603"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1131.0" Y="440.0" GraphRef="a9c25" RelX="-1.0" RelY="-0.018867924528301886" /> <Point X="1144.0" Y="411.0" GraphRef="abf90" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-188191" /> </Interaction> <Interaction GraphId="c1853"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="393.0" Y="496.0" GraphRef="b9950" RelX="1.0400000000000205" RelY="-0.009999999999990905" /> <Point X="396.0" Y="499.0" GraphRef="e6c62" RelX="-1.0" RelY="-0.013333333333333334" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174132" /> </Interaction> <Interaction GraphId="c214c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="809.0" Y="1492.0" GraphRef="cf25f" RelX="0.7799999999999727" RelY="-0.01999999999998181" /> <Point X="812.0" Y="1491.0" GraphRef="cc80a" RelX="-1.0" RelY="-0.04" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-141423" /> </Interaction> <Interaction GraphId="c326f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="569.0" Y="1499.0" GraphRef="df917" RelX="-1.0" RelY="-0.018867924528301886" /> <Point X="184.0" Y="1498.0" GraphRef="a7888" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174070" /> </Interaction> <Interaction GraphId="c45ff"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="802.0" Y="1386.0" GraphRef="de30f" RelX="0.9891891891891892" RelY="0.0" /> <Point X="806.0" Y="1384.0" GraphRef="f7f44" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174255" /> </Interaction> <Interaction GraphId="c48a4"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="516.0" Y="1252.0" GraphRef="bf661" RelX="0.9823008849557522" RelY="0.0" /> <Point X="841.0" Y="1384.0" GraphRef="f5988" RelX="3.0" RelY="0.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174255" /> </Interaction> <Interaction GraphId="c5850"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="407.0" Y="282.0" GraphRef="f064d" RelX="-7.3700000000000045" RelY="-1.2900000000000205" /> <Point X="369.0" Y="356.0" GraphRef="d3072" RelX="1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-188191" /> </Interaction> <Interaction GraphId="c60f1"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="958.0" Y="1491.0" GraphRef="cc80a" RelX="0.9863945578231292" RelY="-0.04" /> <Point X="1021.0" Y="1547.0" GraphRef="dfdfa" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174171" /> </Interaction> <Interaction GraphId="c6b02"> <Comment Source="Reactome">Upon release from the kinetochore, Mad2 associates with Cdc20, hBUBR1, and hBUB3 to form the Mitotic Checkpoint Complex (MCC). Assembly of this complex does not depend on kinetochores but this complex can only inhibit APC/C that has undergone mitotic modifications.</Comment> <BiopaxRef>b44</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="605.0" Y="1698.0" /> <Point X="726.0" Y="1618.0" /> <Anchor Position="0.0" Shape="None" GraphId="ed31f" /> <Anchor Position="0.99" Shape="None" GraphId="e739b" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-141437" /> </Interaction> <Interaction GraphId="c7041"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="509.0" Y="610.0" GraphRef="ce5dc" RelX="0.9862068965517241" RelY="-0.030303030303030304" /> <Point X="659.0" Y="607.0" GraphRef="e1039" RelX="-0.5" RelY="0.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174251" /> </Interaction> <Interaction GraphId="c70d0"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1109.0" Y="1678.0" GraphRef="a52a3" RelX="-0.009009009009009009" RelY="-1.0" /> <Point X="1092.0" Y="1675.0" GraphRef="f2f53" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-179421" /> </Interaction> <Interaction GraphId="c7264"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="973.0" Y="1384.0" GraphRef="e745f" RelX="-1.0" RelY="0.0" /> <Point X="941.0" Y="1410.0" GraphRef="e100b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174104" /> </Interaction> <Interaction GraphId="c7758"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="806.0" Y="1406.0" GraphRef="f9e9e" RelX="-1.3500000000000227" RelY="-0.03999999999996362" /> <Point X="802.0" Y="1386.0" GraphRef="de30f" RelX="0.9891891891891892" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174104" /> </Interaction> <Interaction GraphId="c787f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1398.0" Y="1379.0" GraphRef="db9e5" RelX="-0.009999999999990905" RelY="0.9500000000000455" /> <Point X="1399.0" Y="1382.0" GraphRef="ba077" RelX="-0.007633587786259542" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174120" /> </Interaction> <Interaction GraphId="c89ab"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="897.0" Y="1692.0" GraphRef="f1296" RelX="0.979381443298969" RelY="-0.018867924528301886" /> <Point X="1006.0" Y="1692.0" GraphRef="cc8bb" RelX="2.0" RelY="-1.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-179417" /> </Interaction> <Interaction GraphId="c8bc4"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="348.0" Y="632.0" GraphRef="bb8ff" RelX="1.0" RelY="0.0" /> <Point X="438.0" Y="807.0" GraphRef="d71e2" RelX="-7.5" RelY="0.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174174" /> </Interaction> <Interaction GraphId="c9988"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1131.0" Y="1297.0" GraphRef="d31dd" RelX="-0.029999999999972715" RelY="-0.7699999999999818" /> <Point X="1210.0" Y="1191.0" GraphRef="cb4bb" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174157" /> </Interaction> <Interaction GraphId="c9eaa"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="752.0" Y="1565.0" GraphRef="be265" RelX="-0.009345794392523364" RelY="-1.0" /> <Point X="731.0" Y="1494.0" GraphRef="becad" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-141423" /> </Interaction> <Interaction GraphId="ca1c8"> <Comment Source="Reactome">RB1-dependent polyubiquitination of SKP2 by the APC/C:Cdh1 complex is an important mechanism of RB1-mediated cell cycle exit, which contributes to the RB1 tumor suppressive role. ABC/C:Cdh1-mediated polyubiquitination targets SKP2 for proteasome-mediated degradation. RB1 and APC/C:Cdh1-dependent degradation of SKP2 allows accumulation of CDKN1B (p27Kip1) in the cell, as CDKN1B is a target of the SKP2-containing SCF ubiquitin ligase complex. CDKN1B acts as a CDK inhibitor, enabling mitotic exit (Ji et al. 2004, Binne et al. 2007).</Comment> <BiopaxRef>d5f</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1379.0" Y="532.0" /> <Point X="1243.0" Y="470.0" /> <Anchor Position="0.0" Shape="None" GraphId="d5032" /> <Anchor Position="0.99" Shape="None" GraphId="d9536" /> <Anchor Position="0.5" Shape="None" GraphId="c907c" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-9686969" /> </Interaction> <Interaction GraphId="ca98b"> <Comment Source="Reactome">In the sequestration model, the Mad2 molecules that dissociate from unattached kinetochores are perceived to bind to Cdc20, a protein that recruits specific substrates to the APC/C. Consequently, Mad2 indirectly inhibits the APC/C by sequestering its activator, Cdc20. This requires interaction between Mad1 and Mad2. Cdc20 and Mad1 bind to the same site on Mad2.</Comment> <BiopaxRef>c6e</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="537.0" Y="1620.0" /> <Point X="480.0" Y="1622.0" /> <Anchor Position="0.0" Shape="None" GraphId="e659a" /> <Anchor Position="0.99" Shape="None" GraphId="dd97e" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-141429" /> </Interaction> <Interaction GraphId="cac62"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="296.0" Y="1519.0" GraphRef="bd731" RelX="-0.009174311926605505" RelY="-1.0" /> <Point X="268.0" Y="1409.0" GraphRef="febe3" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174088" /> </Interaction> <Interaction GraphId="cb178"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="462.0" Y="1365.0" GraphRef="c42e7" RelX="0.0" RelY="-0.4600000000000364" /> <Point X="462.0" Y="1362.0" GraphRef="c48dc" RelX="-0.007518796992481203" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174195" /> </Interaction> <Interaction GraphId="cb548"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="582.0" Y="395.0" GraphRef="c6091" RelX="0.5499999999999545" RelY="0.01999999999998181" /> <Point X="605.0" Y="411.0" GraphRef="e5a3e" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174079" /> </Interaction> <Interaction GraphId="cc688"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="958.0" Y="1491.0" GraphRef="cc80a" RelX="0.9863945578231292" RelY="-0.04" /> <Point X="910.0" Y="1430.0" GraphRef="c4005" RelX="36.5" RelY="22.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174104" /> </Interaction> <Interaction GraphId="ccf5c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1323.0" Y="389.0" GraphRef="c7bed" RelX="0.22000000000002728" RelY="1.0600000000000023" /> <Point X="1325.0" Y="392.0" GraphRef="c4b30" RelX="0.0" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-9686980" /> </Interaction> <Interaction GraphId="cd18f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="870.0" Y="1383.0" GraphRef="f8be8" RelX="0.6399999999999864" RelY="-0.009999999999990905" /> <Point X="973.0" Y="1384.0" GraphRef="e745f" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174255" /> </Interaction> <Interaction GraphId="ce8c3"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="160.0" Y="1788.0" GraphRef="b2353" RelX="-0.024390243902439025" RelY="-1.0" /> <Point X="187.0" Y="1756.0" GraphRef="f8823" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174124" /> </Interaction> <Interaction GraphId="cf3e1"> <Comment Source="Reactome">SKP2 is degraded by the anaphase promoting complex/Cyclosome and its activator FZR1 (Cdh1) [APC/C(Cdh1)] (Bashir et al, 2004; Wei et al, 2004). The tight regulation of APC/C(Cdh1) activity ensures the timely elimination SKP2 and, thus, plays a critical role in controlling the M/G1 transition (mitotic exit). APC/C:Cdh1-mediated degradation of SKP2 depends on RB1, as RB1 recruits SKP2 to the APC/C:Cdh1 complex, by simultaneously interacting with SKP2 and FZR1. RB1 does not undergo APC/C:Cdh1-mediated ubiquitination (Binne et al. 2007).</Comment> <BiopaxRef>b79</BiopaxRef> <BiopaxRef>d5f</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1144.0" Y="411.0" /> <Point X="407.0" Y="282.0" /> <Anchor Position="0.0" Shape="None" GraphId="abf90" /> <Anchor Position="0.99" Shape="None" GraphId="f064d" /> <Anchor Position="0.5" Shape="None" GraphId="c5ca1" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-188191" /> </Interaction> <Interaction GraphId="d0cd3"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1261.0" Y="1173.0" GraphRef="cb4bb" RelX="-0.009708737864077669" RelY="-1.0" /> <Point X="1287.0" Y="1146.0" GraphRef="cf529" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174121" /> </Interaction> <Interaction GraphId="d105e"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="461.0" Y="719.0" GraphRef="b3bdd" RelX="0.5600000000000023" RelY="0.0" /> <Point X="525.0" Y="661.0" GraphRef="d2959" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174122" /> </Interaction> <Interaction GraphId="d13fc"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="355.0" Y="696.0" GraphRef="a060f" RelX="1.0" RelY="0.0" /> <Point X="405.0" Y="719.0" GraphRef="fe517" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174122" /> </Interaction> <Interaction GraphId="d1db6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="407.0" Y="282.0" GraphRef="f064d" RelX="-7.3700000000000045" RelY="-1.2900000000000205" /> <Point X="1047.0" Y="318.0" GraphRef="afcba" RelX="-1.0" RelY="-0.047619047619047616" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-188191" /> </Interaction> <Interaction GraphId="d23b5"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="932.0" Y="1632.0" GraphRef="b5572" RelX="0.0" RelY="1.0" /> <Point X="957.0" Y="1693.0" GraphRef="a139e" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-179417" /> </Interaction> <Interaction GraphId="d2f3a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="940.0" Y="674.0" GraphRef="fa918" RelX="0.9400000000000546" RelY="0.0" /> <Point X="943.0" Y="674.0" GraphRef="e1ae8" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174097" /> </Interaction> <Interaction GraphId="d3400"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1325.0" Y="426.0" GraphRef="c4b30" RelX="0.0" RelY="0.9428571428571428" /> <Point X="1379.0" Y="532.0" GraphRef="d5032" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-9686969" /> </Interaction> <Interaction GraphId="d3d29"> <Comment Source="Reactome">At the onset of mitosis, Cdh1 is phosphorylated by Cyclin B-Cdc2 resulting in a conformational change that prevents Cdh1 from activating the APC/C. </Comment> <BiopaxRef>e93</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="659.0" Y="633.0" /> <Point X="660.0" Y="580.0" /> <Anchor Position="0.0" Shape="None" GraphId="a93b1" /> <Anchor Position="0.99" Shape="None" GraphId="cd895" /> <Anchor Position="0.5" Shape="None" GraphId="e1039" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174251" /> </Interaction> <Interaction GraphId="d442a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="954.0" Y="718.0" GraphRef="b7841" RelX="-1.0" RelY="0.0" /> <Point X="921.0" Y="767.0" GraphRef="b34bf" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174235" /> </Interaction> <Interaction GraphId="d4c5d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1092.0" Y="1545.0" GraphRef="f1961" RelX="0.7100000000000364" RelY="-0.01999999999998181" /> <Point X="1095.0" Y="1545.0" GraphRef="b00d3" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174171" /> </Interaction> <Interaction GraphId="d5f7f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="660.0" Y="580.0" GraphRef="cd895" RelX="0.009999999999990905" RelY="-0.5299999999999727" /> <Point X="687.0" Y="544.0" GraphRef="cf93a" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174251" /> </Interaction> <Interaction GraphId="d6548"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1231.0" Y="1050.0" GraphRef="baf08" RelX="-1.0" RelY="0.0" /> <Point X="1033.0" Y="1033.0" GraphRef="bb861" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174144" /> </Interaction> <Interaction GraphId="d6f1f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="369.0" Y="356.0" GraphRef="d3072" RelX="1.0" RelY="0.0" /> <Point X="1301.0" Y="283.0" GraphRef="dd090" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-9686980" /> </Interaction> <Interaction GraphId="d6fb7"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="897.0" Y="1692.0" GraphRef="f1296" RelX="0.979381443298969" RelY="-0.018867924528301886" /> <Point X="957.0" Y="1693.0" GraphRef="a139e" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-179417" /> </Interaction> <Interaction GraphId="d7598"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="314.0" Y="1410.0" GraphRef="d6c05" RelX="0.45999999999997954" RelY="0.009999999999990905" /> <Point X="317.0" Y="1411.0" GraphRef="e6067" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174088" /> </Interaction> <Interaction GraphId="d78ae"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="659.0" Y="990.0" GraphRef="a124a" RelX="-0.009900990099009901" RelY="-1.0" /> <Point X="659.0" Y="951.0" GraphRef="f2ce0" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174159" /> </Interaction> <Interaction GraphId="d8855"> <Comment Source="Reactome">Cyclin A-Cdk2 prevents unscheduled APC reactivation during S phase by binding and subsequently phosphorylating Cdh1. Phosphorylation-dependent dissociation of the Cdh1-activating subunit inhibits the APC/C.</Comment> <BiopaxRef>e13</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="314.0" Y="409.0" /> <Point X="375.0" Y="409.0" /> <Anchor Position="0.0" Shape="None" GraphId="b0540" /> <Anchor Position="0.99" Shape="None" GraphId="b629c" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-188371" /> </Interaction> <Interaction GraphId="d9013"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="461.0" Y="719.0" GraphRef="b3bdd" RelX="0.5600000000000023" RelY="0.0" /> <Point X="529.0" Y="729.0" GraphRef="f4a60" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174122" /> </Interaction> <Interaction GraphId="d9345"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="524.0" Y="951.0" GraphRef="ec5df" RelX="-1.3500000000000227" RelY="0.0" /> <Point X="521.0" Y="951.0" GraphRef="e3b03" RelX="1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174159" /> </Interaction> <Interaction GraphId="d944a"> <Comment Source="Reactome">Following ubiquitination, securin is degraded by the 26S proteasome.</Comment> <BiopaxRef>f71</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="863.0" Y="1090.0" /> <Point X="864.0" Y="1188.0" /> <Anchor Position="0.0" Shape="None" GraphId="ffa8b" /> <Anchor Position="0.99" Shape="None" GraphId="e4100" /> <Anchor Position="0.5" Shape="None" GraphId="d977a" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174202" /> </Interaction> <Interaction GraphId="da7b4"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="497.0" Y="349.0" GraphRef="ed996" RelX="1.0" RelY="0.0" /> <Point X="527.0" Y="393.0" GraphRef="c48f1" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174079" /> </Interaction> <Interaction GraphId="dab57"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1312.0" Y="1191.0" GraphRef="cb4bb" RelX="0.9805825242718447" RelY="0.0" /> <Point X="1316.0" Y="1199.0" GraphRef="c9d51" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174224" /> </Interaction> <Interaction GraphId="db154"> <Comment Source="Reactome">Securin is ubiquitinated by APC/C:Cdc20 (Hagting et al., 2002; Jin et al. 2008).</Comment> <BiopaxRef>f71</BiopaxRef> <BiopaxRef>cb8</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1033.0" Y="1033.0" /> <Point X="906.0" Y="1054.0" /> <Anchor Position="0.0" Shape="None" GraphId="bb861" /> <Anchor Position="0.99" Shape="None" GraphId="d234f" /> <Anchor Position="0.5" Shape="None" GraphId="fe023" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174144" /> </Interaction> <Interaction GraphId="db7e4"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1210.0" Y="1191.0" GraphRef="cb4bb" RelX="-1.0" RelY="0.0" /> <Point X="994.0" Y="1054.0" GraphRef="fe023" RelX="24.5" RelY="10.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174144" /> </Interaction> <Interaction GraphId="db83f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="853.0" Y="716.0" GraphRef="e4b56" RelX="1.0" RelY="0.0" /> <Point X="921.0" Y="767.0" GraphRef="b34bf" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174235" /> </Interaction> <Interaction GraphId="dc1dc"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1264.0" Y="1489.0" GraphRef="aac29" RelX="3.019999999999982" RelY="-0.009999999999990905" /> <Point X="1261.0" Y="1209.0" GraphRef="cb4bb" RelX="-0.009708737864077669" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174238" /> </Interaction> <Interaction GraphId="dc257"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1537.0" Y="1204.0" GraphRef="fc187" RelX="2.2100000000000364" RelY="0.049999999999954525" /> <Point X="709.0" Y="1499.0" GraphRef="df917" RelX="0.9858156028368794" RelY="-0.018867924528301886" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174224" /> </Interaction> <Interaction GraphId="dc45d"> <Comment Source="Reactome">Rape et al. have recently demonstrated that the order in which APC/C targeted proteins are degraded is determined by the processivity of multiubiquitination of these substrates. Processive substrates acquire a polyubiquitin chain upon binding to the APC/C once and are degraded. Distributive substrates bind, dissociate and reassociate with the APC/C multiple times before acquiring an ubiquitin chain of sufficient length to insure degradation. In addition, distributive substrates that dissociate from the APC/C with short ubiquitin chains are targeted for deubiquitination (Rape et al., 2006). Paradoxically, although the multiubiquitination of cyclin A is distributive and later substrates of APC-Cdc20 such as Securin are processive (Rape et al., 2006), Cyclin A is degraded prior to Securin and Cyclin B. The mechanisms insuring this order have not yet be determined.</Comment> <BiopaxRef>a11</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="941.0" Y="1410.0" /> <Point X="806.0" Y="1406.0" /> <Anchor Position="0.0" Shape="None" GraphId="e100b" /> <Anchor Position="0.99" Shape="None" GraphId="f9e9e" /> <Anchor Position="0.5" Shape="None" GraphId="c4005" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174104" /> </Interaction> <Interaction GraphId="dd904"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="604.0" Y="1593.0" GraphRef="e3323" RelX="-0.0196078431372549" RelY="1.0" /> <Point X="605.0" Y="1698.0" GraphRef="ed31f" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-141437" /> </Interaction> <Interaction GraphId="decf3"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1340.0" Y="1161.0" GraphRef="a9a9f" RelX="-1.0" RelY="0.0" /> <Point X="1287.0" Y="1146.0" GraphRef="cf529" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174121" /> </Interaction> <Interaction GraphId="df182"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="407.0" Y="282.0" GraphRef="f064d" RelX="-7.3700000000000045" RelY="-1.2900000000000205" /> <Point X="781.0" Y="407.0" GraphRef="f1665" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-188191" /> </Interaction> <Interaction GraphId="df2e9"> <Comment Source="Reactome">Following multiubiquitination, Cyclin A is targeted for destruction by the 26S proteasome.</Comment> <BiopaxRef>a11</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="806.0" Y="1384.0" /> <Point X="870.0" Y="1383.0" /> <Anchor Position="0.0" Shape="None" GraphId="f7f44" /> <Anchor Position="0.99" Shape="None" GraphId="f8be8" /> <Anchor Position="0.5" Shape="None" GraphId="f5988" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174255" /> </Interaction> <Interaction GraphId="df3ca"> <Comment Source="Reactome">The phosphorylation of Emi1 by Plk1 is believed to be involved in the degradation of Emi1 during mitosis. Plk1 phosphorylates serine residues in the DSGxxS degron sequence of Emi1 recruiting the SCF(betaTrCP) ubiquitin ligase.</Comment> <BiopaxRef>ab0</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="409.0" Y="807.0" /> <Point X="482.0" Y="807.0" /> <Anchor Position="0.0" Shape="None" GraphId="a7726" /> <Anchor Position="0.99" Shape="None" GraphId="a2204" /> <Anchor Position="0.5" Shape="None" GraphId="d71e2" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174174" /> </Interaction> <Interaction GraphId="df743"> <Comment Source="Reactome">Emi1 promotes the accumulation of Cyclin A and entry into S phase by associating with and inhibiting the APC/C:Cdh1 complex at G1/S.</Comment> <BiopaxRef>fd2</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="846.0" Y="674.0" /> <Point X="940.0" Y="674.0" /> <Anchor Position="0.0" Shape="None" GraphId="de10f" /> <Anchor Position="0.99" Shape="None" GraphId="fa918" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174097" /> </Interaction> <Interaction GraphId="dfdc7"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="584.0" Y="1659.0" GraphRef="a1efd" RelX="1.0" RelY="-0.02702702702702703" /> <Point X="605.0" Y="1698.0" GraphRef="ed31f" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-141437" /> </Interaction> <Interaction GraphId="e15b3"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="658.0" Y="1048.0" GraphRef="e7a7d" RelX="-0.009999999999990905" RelY="-0.5599999999999454" /> <Point X="659.0" Y="1044.0" GraphRef="a124a" RelX="-0.009900990099009901" RelY="0.9636363636363636" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174209" /> </Interaction> <Interaction GraphId="e484b"> <Comment Source="Reactome">At the beginning of this reaction, 1 molecule of 'multiubiquitinated Cdh1 associated with APC/C' is present. At the end of this reaction, 1 molecule of 'phosphorylated anaphase promoting complex (APC/C)', and 3 molecules of 'ubiquitin' are present.&lt;br&gt;&lt;br&gt; This reaction takes place in the 'nucleoplasm' and is mediated by the 'endopeptidase activity' of '26S proteasome'.&lt;br&gt;</Comment> <BiopaxRef>d6f</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="965.0" Y="448.0" /> <Point X="851.0" Y="466.0" /> <Anchor Position="0.0" Shape="None" GraphId="fc55a" /> <Anchor Position="0.99" Shape="None" GraphId="a7487" /> <Anchor Position="0.5" Shape="None" GraphId="e9fa9" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174058" /> </Interaction> <Interaction GraphId="e5565"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="870.0" Y="1383.0" GraphRef="f8be8" RelX="0.6399999999999864" RelY="-0.009999999999990905" /> <Point X="864.0" Y="1317.0" GraphRef="aa50a" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174255" /> </Interaction> <Interaction GraphId="e5fa9"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="221.0" Y="1727.0" GraphRef="d0f43" RelX="-1.0" RelY="0.0" /> <Point X="188.0" Y="1727.0" GraphRef="b617f" RelX="0.5" RelY="4.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174124" /> </Interaction> <Interaction GraphId="e601b"> <Comment Source="Reactome">In late mitosis, Cdc20 dissociates from the APC/C and is replaced by the activator Cdh1 (Ballabeni et al. 2011).</Comment> <BiopaxRef>b66</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1316.0" Y="1199.0" /> <Point X="1537.0" Y="1204.0" /> <Anchor Position="0.0" Shape="None" GraphId="c9d51" /> <Anchor Position="0.99" Shape="None" GraphId="fc187" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174224" /> </Interaction> <Interaction GraphId="e62a7"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1261.0" Y="1209.0" GraphRef="cb4bb" RelX="-0.009708737864077669" RelY="1.0" /> <Point X="1249.0" Y="1407.0" GraphRef="fbbbe" RelX="6.0" RelY="-0.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174227" /> </Interaction> <Interaction GraphId="e7353"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="582.0" Y="395.0" GraphRef="c6091" RelX="0.5499999999999545" RelY="0.01999999999998181" /> <Point X="611.0" Y="360.0" GraphRef="e0f00" RelX="-0.02564102564102564" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174079" /> </Interaction> <Interaction GraphId="e76ec"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="551.0" Y="1641.0" GraphRef="a1efd" RelX="0.0" RelY="-1.0" /> <Point X="537.0" Y="1620.0" GraphRef="e659a" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-141429" /> </Interaction> <Interaction GraphId="e779b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="437.0" Y="626.0" GraphRef="ce5dc" RelX="-0.006896551724137931" RelY="0.9393939393939394" /> <Point X="433.0" Y="719.0" GraphRef="a1bf9" RelX="0.0" RelY="0.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174122" /> </Interaction> <Interaction GraphId="e828d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1131.0" Y="1297.0" GraphRef="d31dd" RelX="-0.029999999999972715" RelY="-0.7699999999999818" /> <Point X="964.0" Y="1317.0" GraphRef="aa50a" RelX="0.9801980198019802" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174157" /> </Interaction> <Interaction GraphId="e8b05"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="741.0" Y="952.0" GraphRef="a3f6a" RelX="-1.0" RelY="0.0" /> <Point X="659.0" Y="951.0" GraphRef="f2ce0" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174159" /> </Interaction> <Interaction GraphId="e913d"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1131.0" Y="1297.0" GraphRef="d31dd" RelX="-0.029999999999972715" RelY="-0.7699999999999818" /> <Point X="905.0" Y="1251.0" GraphRef="e4634" RelX="0.9753086419753086" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174157" /> </Interaction> <Interaction GraphId="e9720"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="561.0" Y="1175.0" GraphRef="ffdd4" RelX="1.0299999999999727" RelY="1.9600000000000364" /> <Point X="560.0" Y="1127.0" GraphRef="c7cc5" RelX="-0.009708737864077669" RelY="1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174203" /> </Interaction> <Interaction GraphId="ea07c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="968.0" Y="443.0" GraphRef="af295" RelX="-1.0" RelY="0.0" /> <Point X="965.0" Y="448.0" GraphRef="fc55a" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174058" /> </Interaction> <Interaction GraphId="ea221"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="404.0" Y="1252.0" GraphRef="bf661" RelX="-1.0" RelY="0.0" /> <Point X="371.0" Y="1330.0" GraphRef="e3c9a" RelX="3.0" RelY="0.5" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174105" /> </Interaction> <Interaction GraphId="ea69b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1264.0" Y="1489.0" GraphRef="aac29" RelX="3.019999999999982" RelY="-0.009999999999990905" /> <Point X="1264.0" Y="1553.0" GraphRef="e47fa" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174238" /> </Interaction> <Interaction GraphId="ea906"> <Comment Source="Reactome">In the direct inhibition model, association of the MCC with APCC results in the inactivation of APC/C. However, the affinity between MCC and APC/C is not high, so that the inhibition is readily reversible. The role of unattached kinetochores is to sensitize the APC/C to prolonged inhibition by the MCC.</Comment> <BiopaxRef>b44</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="731.0" Y="1494.0" /> <Point X="809.0" Y="1492.0" /> <Anchor Position="0.0" Shape="None" GraphId="becad" /> <Anchor Position="0.99" Shape="None" GraphId="cf25f" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-141423" /> </Interaction> <Interaction GraphId="eaa35"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="188.0" Y="1689.0" GraphRef="f0545" RelX="0.009999999999990905" RelY="-0.6700000000000728" /> <Point X="244.0" Y="1658.0" GraphRef="f7b91" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174124" /> </Interaction> <Interaction GraphId="eb55c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="644.0" Y="656.0" GraphRef="ac01f" RelX="1.0" RelY="0.0" /> <Point X="659.0" Y="633.0" GraphRef="a93b1" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174251" /> </Interaction> <Interaction GraphId="ec093"> <Comment Source="Reactome">Following its dephosphorylation in late mitosis, Cdh1 replaces Cdc20 as the APC/C activator.</Comment> <BiopaxRef>dc6</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="184.0" Y="1498.0" /> <Point X="219.0" Y="1355.0" /> <Anchor Position="0.0" Shape="None" GraphId="a7888" /> <Anchor Position="0.99" Shape="None" GraphId="baa90" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174070" /> </Interaction> <Interaction GraphId="ed6a6"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="375.0" Y="409.0" GraphRef="b629c" RelX="0.6100000000000136" RelY="0.0" /> <Point X="378.0" Y="409.0" GraphRef="b2ad7" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-188371" /> </Interaction> <Interaction GraphId="eda36"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="516.0" Y="1252.0" GraphRef="bf661" RelX="0.9823008849557522" RelY="0.0" /> <Point X="864.0" Y="1160.0" GraphRef="d977a" RelX="0.5" RelY="21.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174202" /> </Interaction> <Interaction GraphId="edb83"> <Comment Source="Reactome">One model ( the direct inhibition model) describing the inhibition of the APC/C during the mitotic spindle checkpoint suggests that the association of the hBUBR1:hBUB3:MAD2*:CDC20 mitotic checkpoint complex (MCC) with APC/C results in the inactivation of APC/C. The affinity between MCC and APC/C is not high, thus inhibition is readily reversible when the mitotic spindle checkpoint has been satisfied.</Comment> <BiopaxRef>b44</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="962.0" Y="1490.0" /> <Point X="1264.0" Y="1489.0" /> <Anchor Position="0.0" Shape="None" GraphId="f431b" /> <Anchor Position="0.99" Shape="None" GraphId="aac29" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174238" /> </Interaction> <Interaction GraphId="eec14"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1051.0" Y="1693.0" GraphRef="dd066" RelX="0.9400000000000546" RelY="0.0" /> <Point X="1054.0" Y="1696.0" GraphRef="a52a3" RelX="-1.0" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-179417" /> </Interaction> <Interaction GraphId="f0191"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="921.0" Y="828.0" GraphRef="a9de6" RelX="0.0" RelY="0.6100000000000136" /> <Point X="921.0" Y="831.0" GraphRef="b7326" RelX="-0.010526315789473684" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174235" /> </Interaction> <Interaction GraphId="f0510"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="951.0" Y="376.0" GraphRef="c0f2d" RelX="0.9823008849557522" RelY="0.0" /> <Point X="901.0" Y="455.0" GraphRef="e9fa9" RelX="-7.0" RelY="-2.0" ArrowHead="mim-catalysis" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174058" /> </Interaction> <Interaction GraphId="f0ed2"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1095.0" Y="1545.0" GraphRef="b00d3" RelX="-1.0" RelY="0.0" /> <Point X="941.0" Y="1410.0" GraphRef="e100b" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174104" /> </Interaction> <Interaction GraphId="f187f"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="188.0" Y="1689.0" GraphRef="f0545" RelX="0.009999999999990905" RelY="-0.6700000000000728" /> <Point X="168.0" Y="1662.0" GraphRef="bd825" RelX="0.9354838709677419" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174124" /> </Interaction> <Interaction GraphId="f288a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="871.0" Y="510.0" GraphRef="beb00" RelX="-1.0" RelY="0.0" /> <Point X="868.0" Y="509.0" GraphRef="a71c1" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174139" /> </Interaction> <Interaction GraphId="f306b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="458.0" Y="976.0" GraphRef="e3b03" RelX="0.0" RelY="1.0" /> <Point X="458.0" Y="979.0" GraphRef="c9446" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174203" /> </Interaction> <Interaction GraphId="f311a"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1136.0" Y="1377.0" GraphRef="b04f7" RelX="0.0" RelY="-1.0" /> <Point X="1134.0" Y="1374.0" GraphRef="d20ae" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174157" /> </Interaction> <Interaction GraphId="f3145"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="696.0" Y="1111.0" GraphRef="a56f6" RelX="-1.0" RelY="-0.02127659574468085" /> <Point X="659.0" Y="1104.0" GraphRef="c4665" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174209" /> </Interaction> <Interaction GraphId="f329b"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="870.0" Y="1383.0" GraphRef="f8be8" RelX="0.6399999999999864" RelY="-0.009999999999990905" /> <Point X="885.0" Y="1479.0" GraphRef="cc80a" RelX="-0.006802721088435374" RelY="-1.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174255" /> </Interaction> <Interaction GraphId="f3707"> <Comment Source="Reactome">The pocket domain of the RB1 tumor suppressor protein binds to the N-terminal domain of SKP2, a component of the SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex, whose targets include the cyclin-dependent kinase (CDK) inhibitor p27Kip1 (CDKN1B) (Ji et al. 2004, Binne et al. 2007). RB1 is able to simultanously interact with SKP2 and with FZR1 (Cdh1). FZR1 is a substrate-specific adapter for the anaphase promoting complex/cyclosome (APC/C). The interaction with FZR1 involves a different subregion of the pocket domain than the interaction with SKP2, and is partially dependent on the LxCxE binding cleft (Binne et al. 2007).</Comment> <BiopaxRef>a41</BiopaxRef> <BiopaxRef>d5f</BiopaxRef> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="1301.0" Y="283.0" /> <Point X="1323.0" Y="389.0" /> <Anchor Position="0.0" Shape="None" GraphId="dd090" /> <Anchor Position="0.99" Shape="None" GraphId="c7bed" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-9686980" /> </Interaction> <Interaction GraphId="f39ce"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="660.0" Y="580.0" GraphRef="cd895" RelX="0.009999999999990905" RelY="-0.5299999999999727" /> <Point X="633.0" Y="550.0" GraphRef="afe00" RelX="0.9487179487179487" RelY="0.0" ArrowHead="Arrow" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174251" /> </Interaction> <Interaction GraphId="f3a2c"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="813.0" Y="952.0" GraphRef="a3f6a" RelX="0.9726027397260274" RelY="0.0" /> <Point X="1033.0" Y="1033.0" GraphRef="bb861" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174144" /> </Interaction> <Interaction GraphId="f43d3"> <Graphics ConnectorType="Segmented" ZOrder="12288" LineThickness="1.0"> <Point X="500.0" Y="409.0" GraphRef="b2ad7" RelX="0.983739837398374" RelY="0.0" /> <Point X="527.0" Y="393.0" GraphRef="c48f1" RelX="0.0" RelY="0.0" /> </Graphics> <Xref Database="Reactome" ID="R-HSA-174079" /> </Interaction> <Interaction GraphId="f4592"> <Comment Source="Reactome">Phosphorylation of the APC/C is believed to be required for its activation. 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Value="R-HSA-141410" /> </Group> <Group GroupId="f550c" GraphId="e8ec7" Style="Complex"> <Attribute Key="complex_id" Value="R-HSA-179414" /> </Group> <Group GroupId="be1e9" GraphId="ea6b1" Style="Complex"> <Attribute Key="complex_id" Value="R-HSA-68819" /> </Group> <Group GroupId="ce5c0" GraphId="eb459"> <Attribute Key="complex_id" Value="R-HSA-177332" /> </Group> <Group GroupId="f3f76" GraphId="edd08" Style="Complex"> <Attribute Key="complex_id" Value="R-HSA-174155" /> </Group> <Group GroupId="cfc38" GraphId="f1e37" Style="Complex"> <Attribute Key="complex_id" Value="R-HSA-174191" /> </Group> <Group GroupId="ac73f" GraphId="f7786" Style="Complex"> <Attribute Key="complex_id" Value="R-HSA-188192" /> </Group> <Group GroupId="e2f71" GraphId="f82f3" Style="Complex"> <Attribute Key="complex_id" Value="R-HSA-187952" /> </Group> <Group GroupId="acbf9" GraphId="fb392" Style="Complex"> <Attribute Key="complex_id" Value="R-HSA-174196" /> </Group> <Group GroupId="b494e" GraphId="fc5ae" 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rdf:datatype="http://www.w3.org/2001/XMLSchema#string">11742988</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A-type D-box.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Hames RS, Wattam SL, Yamano H, Bacchieri R, Fry AM.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="d9c"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">16413484</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">The processivity of multiubiquitination by the APC determines the order of substrate degradation.</bp:TITLE> <bp:AUTHORS 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rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Lukas C, Sørensen CS, Kramer E, Santoni-Rugiu E, Lindeneg C, Peters JM, Bartek J, Lukas J.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="b79"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">15014503</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Wei W, Ayad NG, Wan Y, Zhang GJ, Kirschner MW, Kaelin WG.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="c03"> <bp:ID 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rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">The tumour suppressor RASSF1A regulates mitosis by inhibiting the APC-Cdc20 complex.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Song MS, Song SJ, Ayad NG, Chang JS, Lee JH, Hong HK, Lee H, Choi N, Kim J, Kim H, Kim JW, Choi EJ, Kirschner MW, Lim DS.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="ab0"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">15469984</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1.</bp:TITLE> 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rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Ji P, Jiang H, Rekhtman K, Bloom J, Ichetovkin M, Pagano M, Zhu L.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="b53"> <bp:ID rdf:datatype="http://www.w3.org/2001/XMLSchema#string">16648845</bp:ID> <bp:DB rdf:datatype="http://www.w3.org/2001/XMLSchema#string">PubMed</bp:DB> <bp:TITLE rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Early mitotic degradation of Nek2A depends on Cdc20-independent interaction with the APC/C.</bp:TITLE> <bp:AUTHORS rdf:datatype="http://www.w3.org/2001/XMLSchema#string">Hayes MJ, Kimata Y, Wattam SL, Lindon C, Mao G, Yamano H, Fry AM.</bp:AUTHORS> </bp:PublicationXref> <bp:PublicationXref xmlns:bp="http://www.biopax.org/release/biopax-level3.owl#" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" rdf:id="c5f"> <bp:ID 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</bp:PublicationXref> </Biopax> </Pathway>

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