Apoptotic execution phase (Homo sapiens)

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53183046, 494514, 3527255213193712216134815, 3332, 42138891735139914514106, 20, 3134, 50361328261411121120, 24512221415, 40, 474323DFF45:DFF40 complex[nucleoplasm]active caspase-6[nucleoplasm]Caspase-8 dimer[cytosol]active caspase-7[nucleoplasm]endoplasmic reticulum membraneactive caspase-8 [cytosol]importin-alpha:importin-beta[cytosol]active caspase-7[cytosol]nucleoplasmDFF45:DFF40 complex[cytosol]importin-alpha:importin-beta[cytosol]DFF45:DFF40 complex[nucleoplasm]mitochondrial matrixHistone H1 boundchromatin DNA[nucleoplasm]importin-alpha:importin-betacomplex[nucleoplasm]active caspase-3[nucleoplasm]HMGB1/HMGB2[nucleoplasm]caspase-3-cleavedDFF45(117,224):DFF40complex[nucleoplasm]Histone H1 boundchromatin DNA[nucleoplasm]DFF40homodimer/homooligomer[nucleoplasm]DFF cleaved DNA[nucleoplasm]HMGB1/HMGB2- boundchromatin[nucleoplasm]DFF40 homodimer[nucleoplasm]DFF40 associatedwith chromatin[nucleoplasm]DFF:associated withtheimportin-alpha:importin-betacomplex[nucleoplasm]active caspase 3[plasma membrane]active caspase-3[cytosol]Caspase cleavedDFF45 (117)[nucleoplasm]DFF40 homodimer[nucleoplasm]cytosolactive caspase-8 [mitochondrial outermembrane]Caspase-8 dimer[mitochondrial outermembrane]DFF45:DFF40 complex[cytosol]DFF:associated withtheimportin-alpha:importin-betacomplex [cytosol]active caspase-6[cytosol]PKP1VIM(2-85)DFFA(1-?)GSN(27-403)KPNB1 [cytosol]BIRC2(1-372)DFFB [cytosol]PKP1(?-?)APC(1-777)DFF:associated withtheimportin-alpha:importin-betacomplexHMGB1/HMGB2- boundchromatinBCAP31(2-164)PRKCQ(355-706)OCLN(321-522)DFFB [nucleoplasm]BMX(1-242)DFFA(1-?)[nucleoplasm]SATB1PTK2(1-772)CASP7(199-303)[nucleoplasm]TJP1DFFA(1-117)TJP1BIRC2(373-618)unidentified caspaseacting on ZO-1DFF cleaved DNADFFA(225-331)STK24(314-443)unidentified caspaseacting onDesmoplakinDSG3(50-781)CASP6(194-293)[nucleoplasm]caspase 3/caspase 7CDH1(155-750)ROCK1(1-1113)DFFA(1-117)[nucleoplasm]DSG2(?-1118)LMNA-1(231-664)CASP6(194-293)[cytosol]CASP7(23-198)[cytosol]FNTA(2-379)ATPATPCASP3(176-277)[cytosol]DSG1DNM1LADPactive caspase-7DFFB [nucleoplasm]DFFB [nucleoplasm]LMNA-1(1-230)PTK2DFFB [nucleoplasm]ACIN1(1-1093)PLECp-5S-PAK2(1-524)Lamin ACASP3(29-175)[nucleoplasm]GAS2(1-279)Histone H1 boundchromatin DNACASP7(199-303)[cytosol]ADPPRKCD(1-676)TJP2(?-?)BIRC2DFFB [cytosol]caspase-3-cleavedDFF45(117,224):DFF40complexp-T402-PAK2(1-524)DFFA(118-224)[nucleoplasm]CASP8(217-374)[mitochondrial outermembrane]DFF45:DFF40 complexCTNNB1-1(1-115)APC(778-2843)PAK2(1-524)MST4DNADFFA(118-224)DBNL(362-431)DFF:associated withtheimportin-alpha:importin-betacomplexPLEC(1-2395)MAPTPTK2(773-1052)CASP8(385-479)[mitochondrial outermembrane]DSPBCAP31(165-237)BMX(243-675)SPTAN1(1186-2472)DBNL(1-361)LMNB1(1-231)PLEC(2396-4684)VIM(2-259)DFF40homodimer/homooligomerDFFB [nucleoplasm]active caspase-6ADD1(1-633)PAK2(213-524)active caspase-8FNTA(59-379)DSP(?-?)STK24(1-443)VIM(2-429)CASP7(23-198)[nucleoplasm]VIM(430-466)HMGB1 [nucleoplasm]unidentified caspaseacting on ZO-2beta-cateninDFFBactive caspase 3ROCK1(1114-1354)CASP8(385-479)[cytosol]CTNNB1-1(116-376)GAS2(280-313)ADD1CASP3(176-277)[plasma membrane]MAPT(422-758)PRKCQDSG3(782-999)DFFA(225-331)[nucleoplasm]KPNB1 [nucleoplasm]CLSPNGSN(27-782)OCLN(1-320)STK24(1-313)LMNB1(232-586)KPNA1 [nucleoplasm]DFFA(118-331)[nucleoplasm]DBNLACIN1active caspase-3SPTAN1OCLNVIM(260-466)VIM(86-466)PRKCD(1-329)CLSPN(1-1072)ROCK1(1-1354)unidentified caspaseacting onPlakophilin 1CASP3(29-175)[plasma membrane]DFFA(1-?) [cytosol]active caspase-7MST4(306-416)DFF45:DFF40 complexSPTAN1(1-1185)active caspase-3FNTA(1-59)BMXSTK24(1-313)APCMAPT(2-421)BCAP31(238-246)KPNB1 [cytosol]SATB1(255-763)PRKCQ(1-354)DNM1LVIMunidentified caspaseacting on OccludinCDH1(155-882)p-T402-PAK2(213-524)DSG1(50-888)Caspase cleavedDFF45 (117)PRKCD(330-676)importin-alpha:importin-betaunidentified caspaseDSG2CASP6(24-179)[cytosol]CASP3(176-277)[nucleoplasm]active caspase-8HMGB2 [nucleoplasm]MST4(1-305)DFF40 homodimerKPNA1 [cytosol]SATB1(1-254)CLSPN(1073-1332)DSG3active caspase-6DFFA(1-?)[nucleoplasm]DFFBCASP6(24-179)[nucleoplasm]HMGB1/HMGB2p-5S-PAK2(1-212)TJP2DFFA(1-117)[nucleoplasm]ADD1(634-737)CASP8(217-374)[cytosol]DFFA(1-?) [cytosol]DFF40 associatedwith chromatinCDH1(751-882)LMNB1KPNA1 [cytosol]BCAP31(2-245)CASP3(29-175)[cytosol]GAS2ACIN1(1094-1341)GSN(404-782)DFFB [nucleoplasm]DSG1(1-889)7, 442929297, 44292915, 332934, 5029


Description

In the execution phase of apoptosis, effector caspases cleave vital cellular proteins leading to the morphological changes that characterize apoptosis. These changes include destruction of the nucleus and other organelles, DNA fragmentation, chromatin condensation, cell shrinkage and cell detachment and membrane blebbing (reviewed in Fischer et al., 2003).Original Pathway at Reactome: http://www.reactome.org/PathwayBrowser/#DB=gk_current&FOCUS_SPECIES_ID=48887&FOCUS_PATHWAY_ID=75153

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Bibliography

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  1. Kalinowska-Herok M, Widłak P.; ''High mobility group proteins stimulate DNA cleavage by apoptotic endonuclease DFF40/CAD due to HMG-box interactions with DNA.''; PubMed Europe PMC Scholia
  2. Thomsen ND, Koerber JT, Wells JA.; ''Structural snapshots reveal distinct mechanisms of procaspase-3 and -7 activation.''; PubMed Europe PMC Scholia
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  20. Webb SJ, Nicholson D, Bubb VJ, Wyllie AH.; ''Caspase-mediated cleavage of APC results in an amino-terminal fragment with an intact armadillo repeat domain.''; PubMed Europe PMC Scholia
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  26. Clarke CA, Bennett LN, Clarke PR.; ''Cleavage of claspin by caspase-7 during apoptosis inhibits the Chk1 pathway.''; PubMed Europe PMC Scholia
  27. van de Water B, Tijdens IB, Verbrugge A, Huigsloot M, Dihal AA, Stevens JL, Jaken S, Mulder GJ.; ''Cleavage of the actin-capping protein alpha -adducin at Asp-Asp-Ser-Asp633-Ala by caspase-3 is preceded by its phosphorylation on serine 726 in cisplatin-induced apoptosis of renal epithelial cells.''; PubMed Europe PMC Scholia
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  29. Dusek RL, Getsios S, Chen F, Park JK, Amargo EV, Cryns VL, Green KJ.; ''The differentiation-dependent desmosomal cadherin desmoglein 1 is a novel caspase-3 target that regulates apoptosis in keratinocytes.''; PubMed Europe PMC Scholia
  30. Sgorbissa A, Benetti R, Marzinotto S, Schneider C, Brancolini C.; ''Caspase-3 and caspase-7 but not caspase-6 cleave Gas2 in vitro: implications for microfilament reorganization during apoptosis.''; PubMed Europe PMC Scholia
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  32. Browne SJ, MacFarlane M, Cohen GM, Paraskeva C.; ''The adenomatous polyposis coli protein and retinoblastoma protein are cleaved early in apoptosis and are potential substrates for caspases.''; PubMed Europe PMC Scholia
  33. Warby SC, Doty CN, Graham RK, Carroll JB, Yang YZ, Singaraja RR, Overall CM, Hayden MR.; ''Activated caspase-6 and caspase-6-cleaved fragments of huntingtin specifically colocalize in the nucleus.''; PubMed Europe PMC Scholia
  34. Liu X, Zou H, Slaughter C, Wang X.; ''DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis.''; PubMed Europe PMC Scholia
  35. Bojarski C, Weiske J, Schöneberg T, Schröder W, Mankertz J, Schulzke JD, Florian P, Fromm M, Tauber R, Huber O.; ''The specific fates of tight junction proteins in apoptotic epithelial cells.''; PubMed Europe PMC Scholia
  36. Chai J, Wu Q, Shiozaki E, Srinivasula SM, Alnemri ES, Shi Y.; ''Crystal structure of a procaspase-7 zymogen: mechanisms of activation and substrate binding.''; PubMed Europe PMC Scholia
  37. Liu X, Zou H, Widlak P, Garrard W, Wang X.; ''Activation of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease). Oligomerization and direct interaction with histone H1.''; PubMed Europe PMC Scholia
  38. Huang CY, Wu YM, Hsu CY, Lee WS, Lai MD, Lu TJ, Huang CL, Leu TH, Shih HM, Fang HI, Robinson DR, Kung HJ, Yuan CJ.; ''Caspase activation of mammalian sterile 20-like kinase 3 (Mst3). Nuclear translocation and induction of apoptosis.''; PubMed Europe PMC Scholia
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  42. Clem RJ, Sheu TT, Richter BW, He WW, Thornberry NA, Duckett CS, Hardwick JM.; ''c-IAP1 is cleaved by caspases to produce a proapoptotic C-terminal fragment.''; PubMed Europe PMC Scholia
  43. Chen YR, Kori R, John B, Tan TH.; ''Caspase-mediated cleavage of actin-binding and SH3-domain-containing proteins cortactin, HS1, and HIP-55 during apoptosis.''; PubMed Europe PMC Scholia
  44. Shi Y.; ''Mechanisms of caspase activation and inhibition during apoptosis.''; PubMed Europe PMC Scholia
  45. Steinhusen U, Badock V, Bauer A, Behrens J, Wittman-Liebold B, Dörken B, Bommert K.; ''Apoptosis-induced cleavage of beta-catenin by caspase-3 results in proteolytic fragments with reduced transactivation potential.''; PubMed Europe PMC Scholia
  46. Zhivotovsky B, Samali A, Gahm A, Orrenius S.; ''Caspases: their intracellular localization and translocation during apoptosis.''; PubMed Europe PMC Scholia
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  48. Rao L, Perez D, White E.; ''Lamin proteolysis facilitates nuclear events during apoptosis.''; PubMed Europe PMC Scholia
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  50. Breckenridge DG, Stojanovic M, Marcellus RC, Shore GC.; ''Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosol.''; PubMed Europe PMC Scholia
  51. Wu YM, Huang CL, Kung HJ, Huang CY.; ''Proteolytic activation of ETK/Bmx tyrosine kinase by caspases.''; PubMed Europe PMC Scholia
  52. Galande S, Dickinson LA, Mian IS, Sikorska M, Kohwi-Shigematsu T.; ''SATB1 cleavage by caspase 6 disrupts PDZ domain-mediated dimerization, causing detachment from chromatin early in T-cell apoptosis.''; PubMed Europe PMC Scholia
  53. Kim KW, Chung HH, Chung CW, Kim IK, Miura M, Wang S, Zhu H, Moon KD, Rha GB, Park JH, Jo DG, Woo HN, Song YH, Kim BJ, Yuan J, Jung YK.; ''Inactivation of farnesyltransferase and geranylgeranyltransferase I by caspase-3: cleavage of the common alpha subunit during apoptosis.''; PubMed Europe PMC Scholia
  54. Stegh AH, Herrmann H, Lampel S, Weisenberger D, Andrä K, Seper M, Wiche G, Krammer PH, Peter ME.; ''Identification of the cytolinker plectin as a major early in vivo substrate for caspase 8 during CD95- and tumor necrosis factor receptor-mediated apoptosis.''; PubMed Europe PMC Scholia
  55. Kothakota S, Azuma T, Reinhard C, Klippel A, Tang J, Chu K, McGarry TJ, Kirschner MW, Koths K, Kwiatkowski DJ, Williams LT.; ''Caspase-3-generated fragment of gelsolin: effector of morphological change in apoptosis.''; PubMed Europe PMC Scholia
  56. Watt W, Koeplinger KA, Mildner AM, Heinrikson RL, Tomasselli AG, Watenpaugh KD.; ''The atomic-resolution structure of human caspase-8, a key activator of apoptosis.''; PubMed Europe PMC Scholia
  57. Geng YJ, Azuma T, Tang JX, Hartwig JH, Muszynski M, Wu Q, Libby P, Kwiatkowski DJ.; ''Caspase-3-induced gelsolin fragmentation contributes to actin cytoskeletal collapse, nucleolysis, and apoptosis of vascular smooth muscle cells exposed to proinflammatory cytokines.''; PubMed Europe PMC Scholia
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History

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CompareRevisionActionTimeUserComment
114845view16:34, 25 January 2021ReactomeTeamReactome version 75
113291view11:36, 2 November 2020ReactomeTeamReactome version 74
112503view15:46, 9 October 2020ReactomeTeamReactome version 73
101415view11:29, 1 November 2018ReactomeTeamreactome version 66
100953view21:06, 31 October 2018ReactomeTeamreactome version 65
100490view19:40, 31 October 2018ReactomeTeamreactome version 64
100035view16:24, 31 October 2018ReactomeTeamreactome version 63
99588view14:58, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99208view12:43, 31 October 2018ReactomeTeamreactome version 62
93810view13:37, 16 August 2017ReactomeTeamreactome version 61
93352view11:21, 9 August 2017ReactomeTeamreactome version 61
86436view09:18, 11 July 2016ReactomeTeamreactome version 56
83236view10:27, 18 November 2015ReactomeTeamVersion54
81341view12:51, 21 August 2015ReactomeTeamVersion53
76813view08:03, 17 July 2014ReactomeTeamFixed remaining interactions
76517view11:44, 16 July 2014ReactomeTeamFixed remaining interactions
75850view09:50, 11 June 2014ReactomeTeamRe-fixing comment source
75550view10:33, 10 June 2014ReactomeTeamReactome 48 Update
74905view13:43, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74904view12:27, 8 May 2014AnweshaChanged comment source from Wikipathways to WikiPathways
74549view08:35, 30 April 2014ReactomeTeamReactome46
71704view19:56, 17 October 2013MaintBotUpdated data sources
44958view12:40, 6 October 2011MartijnVanIerselOntology Term : 'apoptotic cell death pathway' added !
42155view23:16, 4 March 2011MaintBotModified categories
39997view00:18, 22 January 2011AlexanderPicoreset uniprot
39810view05:50, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACIN1(1-1093)ProteinQ9UKV3 (Uniprot-TrEMBL)
ACIN1(1094-1341)ProteinQ9UKV3 (Uniprot-TrEMBL)
ACIN1ProteinQ9UKV3 (Uniprot-TrEMBL)
ADD1(1-633)ProteinP35611 (Uniprot-TrEMBL)
ADD1(634-737)ProteinP35611 (Uniprot-TrEMBL)
ADD1ProteinP35611 (Uniprot-TrEMBL)
ADPMetaboliteCHEBI:16761 (ChEBI)
APC(1-777)ProteinP25054 (Uniprot-TrEMBL)
APC(778-2843)ProteinP25054 (Uniprot-TrEMBL)
APCProteinP25054 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:15422 (ChEBI)
BCAP31(165-237)ProteinP51572 (Uniprot-TrEMBL)
BCAP31(2-164)ProteinP51572 (Uniprot-TrEMBL)
BCAP31(2-245)ProteinP51572 (Uniprot-TrEMBL)
BCAP31(238-246)ProteinP51572 (Uniprot-TrEMBL)
BIRC2(1-372)ProteinQ13490 (Uniprot-TrEMBL)
BIRC2(373-618)ProteinQ13490 (Uniprot-TrEMBL)
BIRC2ProteinQ13490 (Uniprot-TrEMBL)
BMX(1-242)ProteinP51813 (Uniprot-TrEMBL)
BMX(243-675)ProteinP51813 (Uniprot-TrEMBL)
BMXProteinP51813 (Uniprot-TrEMBL)
CASP3(176-277) [cytosol]ProteinP42574 (Uniprot-TrEMBL)
CASP3(176-277) [nucleoplasm]ProteinP42574 (Uniprot-TrEMBL)
CASP3(176-277) [plasma membrane]ProteinP42574 (Uniprot-TrEMBL)
CASP3(29-175) [cytosol]ProteinP42574 (Uniprot-TrEMBL)
CASP3(29-175) [nucleoplasm]ProteinP42574 (Uniprot-TrEMBL)
CASP3(29-175) [plasma membrane]ProteinP42574 (Uniprot-TrEMBL)
CASP6(194-293) [cytosol]ProteinP55212 (Uniprot-TrEMBL)
CASP6(194-293) [nucleoplasm]ProteinP55212 (Uniprot-TrEMBL)
CASP6(24-179) [cytosol]ProteinP55212 (Uniprot-TrEMBL)
CASP6(24-179) [nucleoplasm]ProteinP55212 (Uniprot-TrEMBL)
CASP7(199-303) [cytosol]ProteinP55210 (Uniprot-TrEMBL)
CASP7(199-303) [nucleoplasm]ProteinP55210 (Uniprot-TrEMBL)
CASP7(23-198) [cytosol]ProteinP55210 (Uniprot-TrEMBL)
CASP7(23-198) [nucleoplasm]ProteinP55210 (Uniprot-TrEMBL)
CASP8(217-374) [cytosol]ProteinQ14790 (Uniprot-TrEMBL)
CASP8(217-374)

[mitochondrial outer

membrane]
ProteinQ14790 (Uniprot-TrEMBL)
CASP8(385-479) [cytosol]ProteinQ14790 (Uniprot-TrEMBL)
CASP8(385-479)

[mitochondrial outer

membrane]
ProteinQ14790 (Uniprot-TrEMBL)
CDH1(155-750)ProteinP12830 (Uniprot-TrEMBL)
CDH1(155-882)ProteinP12830 (Uniprot-TrEMBL)
CDH1(751-882)ProteinP12830 (Uniprot-TrEMBL)
CLSPN(1-1072)ProteinQ9HAW4 (Uniprot-TrEMBL)
CLSPN(1073-1332)ProteinQ9HAW4 (Uniprot-TrEMBL)
CLSPNProteinQ9HAW4 (Uniprot-TrEMBL)
CTNNB1-1(1-115)ProteinP35222-1 (Uniprot-TrEMBL)
CTNNB1-1(116-376)ProteinP35222-1 (Uniprot-TrEMBL)
Caspase cleaved DFF45 (117)ComplexREACT_13101 (Reactome)
DBNL(1-361)ProteinQ9UJU6 (Uniprot-TrEMBL)
DBNL(362-431)ProteinQ9UJU6 (Uniprot-TrEMBL)
DBNLProteinQ9UJU6 (Uniprot-TrEMBL)
DFF cleaved DNAComplexREACT_14657 (Reactome)
DFF40 homodimer/homooligomerREACT_14397 (Reactome)
DFF40 associated with chromatinComplexREACT_14402 (Reactome)
DFF40 homodimerComplexREACT_14622 (Reactome)
DFF45:DFF40 complexComplexREACT_12695 (Reactome)
DFF45:DFF40 complexComplexREACT_14626 (Reactome)
DFF:associated with

the importin-alpha:importin-beta

complex
ComplexREACT_14003 (Reactome)
DFF:associated with

the importin-alpha:importin-beta

complex
ComplexREACT_14680 (Reactome)
DFFA(1-117) [nucleoplasm]ProteinO00273 (Uniprot-TrEMBL)
DFFA(1-117)ProteinO00273 (Uniprot-TrEMBL)
DFFA(1-?) [nucleoplasm]ProteinO00273 (Uniprot-TrEMBL)
DFFA(1-?) [cytosol]ProteinO00273 (Uniprot-TrEMBL)
DFFA(1-?)ProteinO00273 (Uniprot-TrEMBL)
DFFA(118-224) [nucleoplasm]ProteinO00273 (Uniprot-TrEMBL)
DFFA(118-224)ProteinO00273 (Uniprot-TrEMBL)
DFFA(118-331) [nucleoplasm]ProteinO00273 (Uniprot-TrEMBL)
DFFA(225-331) [nucleoplasm]ProteinO00273 (Uniprot-TrEMBL)
DFFA(225-331)ProteinO00273 (Uniprot-TrEMBL)
DFFB [cytosol]ProteinO76075 (Uniprot-TrEMBL)
DFFB [nucleoplasm]ProteinO76075 (Uniprot-TrEMBL)
DFFBProteinO76075 (Uniprot-TrEMBL)
DNAREACT_3913 (Reactome)
DNM1LProteinO00429 (Uniprot-TrEMBL)
DSG1(1-889)ProteinQ02413 (Uniprot-TrEMBL)
DSG1(50-888)ProteinQ02413 (Uniprot-TrEMBL)
DSG1ProteinQ02413 (Uniprot-TrEMBL)
DSG2(?-1118)ProteinQ14126 (Uniprot-TrEMBL) The caspase 3-mediated proteolytic processing of full-length Dsg2, the most widespread desmosomal cadherin, results in disappearance of Dsg2 from the cell surface and appearance of a 70-kDa fragment in the cytosol. Loss of Dsg2 from the cell surface may contribute to the progressive loss of intercellular adhesion strength during apoptosis (Cirillo et al., 2008)
DSG2ProteinQ14126 (Uniprot-TrEMBL)
DSG3(50-781)ProteinP32926 (Uniprot-TrEMBL)
DSG3(782-999)ProteinP32926 (Uniprot-TrEMBL)
DSG3ProteinP32926 (Uniprot-TrEMBL)
DSP(?-?)ProteinP15924 (Uniprot-TrEMBL)
DSPProteinP15924 (Uniprot-TrEMBL)
FNTA(1-59)ProteinP49354 (Uniprot-TrEMBL)
FNTA(2-379)ProteinP49354 (Uniprot-TrEMBL)
FNTA(59-379)ProteinP49354 (Uniprot-TrEMBL)
GAS2(1-279)ProteinO43903 (Uniprot-TrEMBL)
GAS2(280-313)ProteinO43903 (Uniprot-TrEMBL)
GAS2ProteinO43903 (Uniprot-TrEMBL)
GSN(27-403)ProteinP06396 (Uniprot-TrEMBL)
GSN(27-782)ProteinP06396 (Uniprot-TrEMBL)
GSN(404-782)ProteinP06396 (Uniprot-TrEMBL)
HMGB1 [nucleoplasm]ProteinP09429 (Uniprot-TrEMBL)
HMGB1/HMGB2- bound chromatinComplexREACT_14370 (Reactome)
HMGB1/HMGB2ProteinREACT_14288 (Reactome)
HMGB2 [nucleoplasm]ProteinP26583 (Uniprot-TrEMBL)
Histone H1 bound chromatin DNAComplexREACT_14129 (Reactome)
KPNA1 [cytosol]ProteinP52294 (Uniprot-TrEMBL)
KPNA1 [nucleoplasm]ProteinP52294 (Uniprot-TrEMBL)
KPNB1 [cytosol]ProteinQ14974 (Uniprot-TrEMBL)
KPNB1 [nucleoplasm]ProteinQ14974 (Uniprot-TrEMBL)
LMNA-1(1-230)ProteinP02545-1 (Uniprot-TrEMBL)
LMNA-1(231-664)ProteinP02545-1 (Uniprot-TrEMBL)
LMNB1(1-231)ProteinP20700 (Uniprot-TrEMBL)
LMNB1(232-586)ProteinP20700 (Uniprot-TrEMBL)
LMNB1ProteinP20700 (Uniprot-TrEMBL)
Lamin AProteinP02545-1 (Uniprot-TrEMBL)
MAPT(2-421)ProteinP10636 (Uniprot-TrEMBL)
MAPT(422-758)ProteinP10636 (Uniprot-TrEMBL)
MAPTProteinP10636 (Uniprot-TrEMBL)
MST4(1-305)ProteinQ9P289 (Uniprot-TrEMBL)
MST4(306-416)ProteinQ9P289 (Uniprot-TrEMBL)
MST4ProteinQ9P289 (Uniprot-TrEMBL)
OCLN(1-320)ProteinQ16625 (Uniprot-TrEMBL)
OCLN(321-522)ProteinQ16625 (Uniprot-TrEMBL)
OCLNProteinQ16625 (Uniprot-TrEMBL)
PAK2(1-524)ProteinQ13177 (Uniprot-TrEMBL)
PAK2(213-524)ProteinQ13177 (Uniprot-TrEMBL)
PKP1(?-?)ProteinQ13835 (Uniprot-TrEMBL)
PKP1ProteinQ13835 (Uniprot-TrEMBL)
PLEC(1-2395)ProteinQ15149 (Uniprot-TrEMBL)
PLEC(2396-4684)ProteinQ15149 (Uniprot-TrEMBL)
PLECProteinQ15149 (Uniprot-TrEMBL)
PRKCD(1-329)ProteinQ05655 (Uniprot-TrEMBL)
PRKCD(1-676)ProteinQ05655 (Uniprot-TrEMBL)
PRKCD(330-676)ProteinQ05655 (Uniprot-TrEMBL)
PRKCQ(1-354)ProteinQ04759 (Uniprot-TrEMBL)
PRKCQ(355-706)ProteinQ04759 (Uniprot-TrEMBL)
PRKCQProteinQ04759 (Uniprot-TrEMBL)
PTK2(1-772)ProteinQ05397 (Uniprot-TrEMBL)
PTK2(773-1052)ProteinQ05397 (Uniprot-TrEMBL)
PTK2ProteinQ05397 (Uniprot-TrEMBL)
ROCK1(1-1113)ProteinQ13464 (Uniprot-TrEMBL)
ROCK1(1-1354)ProteinQ13464 (Uniprot-TrEMBL)
ROCK1(1114-1354)ProteinQ13464 (Uniprot-TrEMBL)
SATB1(1-254)ProteinQ01826 (Uniprot-TrEMBL)
SATB1(255-763)ProteinQ01826 (Uniprot-TrEMBL)
SATB1ProteinQ01826 (Uniprot-TrEMBL)
SPTAN1(1-1185)ProteinQ13813 (Uniprot-TrEMBL)
SPTAN1(1186-2472)ProteinQ13813 (Uniprot-TrEMBL)
SPTAN1ProteinQ13813 (Uniprot-TrEMBL)
STK24(1-313)ProteinQ9Y6E0 (Uniprot-TrEMBL)
STK24(1-443)ProteinQ9Y6E0 (Uniprot-TrEMBL)
STK24(314-443)ProteinQ9Y6E0 (Uniprot-TrEMBL)
TJP1ProteinQ07157 (Uniprot-TrEMBL)
TJP2(?-?)ProteinQ9UDY2 (Uniprot-TrEMBL)
TJP2ProteinQ9UDY2 (Uniprot-TrEMBL)
VIM(2-259)ProteinP08670 (Uniprot-TrEMBL)
VIM(2-429)ProteinP08670 (Uniprot-TrEMBL)
VIM(2-85)ProteinP08670 (Uniprot-TrEMBL)
VIM(260-466)ProteinP08670 (Uniprot-TrEMBL)
VIM(430-466)ProteinP08670 (Uniprot-TrEMBL)
VIM(86-466)ProteinP08670 (Uniprot-TrEMBL)
VIMProteinP08670 (Uniprot-TrEMBL)
active caspase 3ComplexREACT_12262 (Reactome)
active caspase-3ComplexREACT_13159 (Reactome)
active caspase-3ComplexREACT_2467 (Reactome)
active caspase-6ComplexREACT_14257 (Reactome)
active caspase-6ComplexREACT_14343 (Reactome)
active caspase-7ComplexREACT_14263 (Reactome)
active caspase-7ComplexREACT_3366 (Reactome)
active caspase-8ComplexREACT_151128 (Reactome)
active caspase-8ComplexREACT_161457 (Reactome)
beta-cateninProteinREACT_10304 (Reactome)
caspase 3/caspase 7REACT_12368 (Reactome)
caspase-3-cleaved

DFF45 (117,224):DFF40

complex
ComplexREACT_13244 (Reactome)
importin-alpha:importin-betaComplexREACT_13986 (Reactome)
p-5S-PAK2(1-212)ProteinQ13177 (Uniprot-TrEMBL)
p-5S-PAK2(1-524)ProteinQ13177 (Uniprot-TrEMBL)
p-T402-PAK2(1-524)ProteinQ13177 (Uniprot-TrEMBL)
p-T402-PAK2(213-524)ProteinQ13177 (Uniprot-TrEMBL)
unidentified caspase

acting on

Desmoplakin
REACT_21697 (Reactome)
unidentified caspase

acting on

Plakophilin 1
REACT_21872 (Reactome)
unidentified caspase acting on OccludinREACT_21584 (Reactome)
unidentified caspase acting on ZO-1REACT_22050 (Reactome)
unidentified caspase acting on ZO-2REACT_22003 (Reactome)
unidentified caspaseREACT_14138 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ACIN1(1-1093)ArrowREACT_12450 (Reactome)
ACIN1(1094-1341)ArrowREACT_12450 (Reactome)
ACIN1REACT_12450 (Reactome)
ADD1(1-633)ArrowREACT_12044 (Reactome)
ADD1(634-737)ArrowREACT_12044 (Reactome)
ADD1REACT_12044 (Reactome)
ADPArrowREACT_13431 (Reactome)
ADPArrowREACT_13820 (Reactome)
APC(1-777)ArrowREACT_12012 (Reactome)
APC(778-2843)ArrowREACT_12012 (Reactome)
APCREACT_12012 (Reactome)
ATPREACT_13431 (Reactome)
ATPREACT_13820 (Reactome)
BCAP31(165-237)ArrowREACT_13554 (Reactome)
BCAP31(2-164)ArrowREACT_13554 (Reactome)
BCAP31(2-245)REACT_13554 (Reactome)
BCAP31(238-246)ArrowREACT_13554 (Reactome)
BIRC2(1-372)ArrowREACT_12045 (Reactome)
BIRC2(373-618)ArrowREACT_12045 (Reactome)
BIRC2REACT_12045 (Reactome)
BMX(1-242)ArrowREACT_13417 (Reactome)
BMX(243-675)ArrowREACT_13417 (Reactome)
BMXREACT_13417 (Reactome)
CDH1(155-750)ArrowREACT_12072 (Reactome)
CDH1(155-882)REACT_12072 (Reactome)
CDH1(751-882)ArrowREACT_12072 (Reactome)
CLSPN(1-1072)ArrowREACT_13652 (Reactome)
CLSPN(1073-1332)ArrowREACT_13652 (Reactome)
CLSPNREACT_13652 (Reactome)
CTNNB1-1(1-115)ArrowREACT_12022 (Reactome)
CTNNB1-1(116-376)ArrowREACT_12022 (Reactome)
Caspase cleaved DFF45 (117)ArrowREACT_12544 (Reactome)
Caspase cleaved DFF45 (117)REACT_12404 (Reactome)
DBNL(1-361)ArrowREACT_12025 (Reactome)
DBNL(362-431)ArrowREACT_12025 (Reactome)
DBNLREACT_12025 (Reactome)
DFF cleaved DNAArrowREACT_13702 (Reactome)
DFF40 homodimer/homooligomerArrowREACT_13702 (Reactome)
DFF40 homodimer/homooligomerREACT_13514 (Reactome)
DFF40 associated with chromatinArrowREACT_13514 (Reactome)
DFF40 associated with chromatinREACT_13702 (Reactome)
DFF40 associated with chromatinmim-catalysisREACT_13702 (Reactome)
DFF40 homodimerArrowREACT_13708 (Reactome)
DFF45:DFF40 complexArrowREACT_13679 (Reactome)
DFF45:DFF40 complexREACT_12544 (Reactome)
DFF45:DFF40 complexREACT_13756 (Reactome)
DFF:associated with

the importin-alpha:importin-beta

complex
ArrowREACT_13544 (Reactome)
DFF:associated with

the importin-alpha:importin-beta

complex
ArrowREACT_13756 (Reactome)
DFF:associated with

the importin-alpha:importin-beta

complex
REACT_13544 (Reactome)
DFFA(1-117)ArrowREACT_13689 (Reactome)
DFFA(1-?)REACT_13679 (Reactome)
DFFA(118-224)ArrowREACT_13689 (Reactome)
DFFA(225-331)ArrowREACT_13689 (Reactome)
DFFBArrowREACT_13689 (Reactome)
DFFBREACT_13679 (Reactome)
DFFBREACT_13708 (Reactome)
DNAREACT_13513 (Reactome)
DNM1LArrowREACT_13560 (Reactome)
DNM1LREACT_13560 (Reactome)
DSG1(1-889)ArrowREACT_11997 (Reactome)
DSG1(50-888)ArrowREACT_11997 (Reactome)
DSG1REACT_11997 (Reactome)
DSG2(?-1118)ArrowREACT_13598 (Reactome)
DSG2REACT_13598 (Reactome)
DSG3(50-781)ArrowREACT_12082 (Reactome)
DSG3(782-999)ArrowREACT_12082 (Reactome)
DSG3REACT_12082 (Reactome)
DSP(?-?)ArrowREACT_13605 (Reactome)
DSPREACT_13605 (Reactome)
FNTA(1-59)ArrowREACT_12014 (Reactome)
FNTA(2-379)REACT_12014 (Reactome)
FNTA(59-379)ArrowREACT_12014 (Reactome)
GAS2(1-279)ArrowREACT_12004 (Reactome)
GAS2(280-313)ArrowREACT_12004 (Reactome)
GAS2REACT_12004 (Reactome)
GSN(27-403)ArrowREACT_13795 (Reactome)
GSN(27-782)REACT_13795 (Reactome)
GSN(404-782)ArrowREACT_13795 (Reactome)
HMGB1/HMGB2- bound chromatinArrowREACT_13513 (Reactome)
HMGB1/HMGB2REACT_13513 (Reactome)
Histone H1 bound chromatin DNAREACT_13514 (Reactome)
LMNA-1(1-230)ArrowREACT_13476 (Reactome)
LMNA-1(231-664)ArrowREACT_13476 (Reactome)
LMNB1(1-231)ArrowREACT_13484 (Reactome)
LMNB1(232-586)ArrowREACT_13484 (Reactome)
LMNB1REACT_13484 (Reactome)
Lamin AREACT_13476 (Reactome)
MAPT(2-421)ArrowREACT_13414 (Reactome)
MAPT(422-758)ArrowREACT_13414 (Reactome)
MAPTREACT_13414 (Reactome)
MST4(1-305)ArrowREACT_13636 (Reactome)
MST4(306-416)ArrowREACT_13636 (Reactome)
MST4REACT_13636 (Reactome)
OCLN(1-320)ArrowREACT_13549 (Reactome)
OCLN(321-522)ArrowREACT_13549 (Reactome)
OCLNREACT_13549 (Reactome)
PAK2(1-524)REACT_13431 (Reactome)
PAK2(1-524)mim-catalysisREACT_13431 (Reactome)
PAK2(213-524)ArrowREACT_13747 (Reactome)
PAK2(213-524)REACT_13820 (Reactome)
PAK2(213-524)mim-catalysisREACT_13820 (Reactome)
PKP1(?-?)ArrowREACT_13418 (Reactome)
PKP1REACT_13418 (Reactome)
PLEC(1-2395)ArrowREACT_13522 (Reactome)
PLEC(2396-4684)ArrowREACT_13522 (Reactome)
PLECREACT_13522 (Reactome)
PRKCD(1-329)ArrowREACT_12471 (Reactome)
PRKCD(1-676)REACT_12471 (Reactome)
PRKCD(330-676)ArrowREACT_12471 (Reactome)
PRKCQ(1-354)ArrowREACT_12638 (Reactome)
PRKCQ(355-706)ArrowREACT_12638 (Reactome)
PRKCQREACT_12638 (Reactome)
PTK2(1-772)ArrowREACT_12021 (Reactome)
PTK2(773-1052)ArrowREACT_12021 (Reactome)
PTK2REACT_12021 (Reactome)
REACT_11997 (Reactome) Caspase mediated cleavage of desmoglein 1 leads to decreased expression at the cell surface and re-localization of its C terminus diffusely throughout the cytoplasm. Cleavage is thought to contribute to the dismantling of desmosomes during keratinocyte apoptosis (Dusek et al., 2006).
REACT_12004 (Reactome) Cleavage of Gas2 during apoptosis is associated with changes of the microfilament system but does not interfere with its ability to bind F-actin (Brancolini et al., 1995).
REACT_12012 (Reactome) Cleavage of APC by caspase 3 and release of the amino-terminal fragment (1-760) are required for the APC mediated acceleration of apoptosis-associated caspase activity (Qian et al., 2007).
REACT_12014 (Reactome) Farnesyltransferase/geranyl-geranyltransferase catalyzes the transfer of a farnesyl or geranyl-geranyl moiety from farnesyl or geranyl-geranyl pyrophosphate to a cysteine at the fourth position from the C-terminus of proteins having the C-terminal sequence Cys-aliphatic-aliphatic-X. This enzyme complex consists of a heterodimer of an alpha and a beta subunit. The alpha subunit is thought to function in the formation of a stable complex with the substrate. This alpha subnit is cleaved by caspase 3. Expression of the cleavage product (60-379) induces cell death (Kim et al., 2001).
REACT_12021 (Reactome) FAK is a tyrosine kinase that localizes to focal adhesions and associates temporally and spatially with integrins (see references in Fischer et al., 2003 ). FAK is cleaved by caspases including caspase-7 (Wen et al., 1997). Caspases also cleave fodrin and components of the focal adhesion complex which links cortical actin filaments and membrane proteins to the extracellular matrix. Cleavage of these proteins is thought to promote cell shrinkage and cell detachment and disrupt antiapoptotic integrin signaling (see Fischer et al., 2003).
REACT_12022 (Reactome) Apoptosis-induced cleavage of beta-catenin by caspase 3 results in reduced alpha catenin binding, relocalization to the cytoplasm and a reduction in cell-cell contact. In addition, the resulting proteolytic fragments have reduced transcription factor activity (Steinhusen et al., 2000 ).
REACT_12024 (Reactome) Apoptosis induced caspases cleave cortical actin network components including fodrin and components of the focal adhesion complex components which links membrane proteins and cortical actin filaments to the extracellular matrix (Janicke et al.,1998). Cleavage of these proteins results in disruption of the cortical cytoskeleton and may contribute to membrane blebbing (see Fischer et al., 2003). The full length 240 kDa alpha-fodrin protein can be cleaved at several sites within its sequence by activated caspases to yield amino-terminal 150 kDa, carboxy-terminal 120 kDa and 35 kDa major products. Cleavage of alpha-II fodrin leads to membrane malfunction and cell shrinkage (Janicke et al., 1998).
REACT_12025 (Reactome) HIP-55 is an actin binding SH3 domain protein that is cleaved by caspase-3. Cleavage results in dissociation of the actin-binding domain from the SH3 domain and may alter cell signaling to and from the actin cytoskeleton. In addition, this cleavage may be involved in the the alteration in cell morphology that occur during apoptosis (Chen et al., 2001).
REACT_12044 (Reactome) The cortical actin cytoskeletal network is lost during apoptosis. During apoptosis, increased phosphorylation of the actin capping protein alpha-adducin leads to its dissociation from the cytoskeleton. The caspase-3-mediated cleavage cleavage of alpha adducin at Asp-Asp-Ser-Asp(633)-Ala prevents its reassociation (van de Water et al, 2000).
REACT_12045 (Reactome) c-IAP1 is cleaved by caspase-3 producing a proapoptotic C-terminal fragment.
REACT_12072 (Reactome) The cleavage of E-cadherin at both the intracellular and extracellular domains likely contributes to the disruption of cadherin-mediated cell-cell contacts in apoptotic cells. Loss of cell contact is necessary for cell rounding and exit from the epithelium (Steinhusen et al., 2001).
REACT_12082 (Reactome) In epithelial cells, desmosomes are anchoring junctions that mediate strong cell-cell contacts. Desmosomal proteins are proteolytically targeted during apoptosis (Weiske et al., 2001). Desmogleins are a major component of the desmosome are specifically cleaved after onset of apoptosis. Cleavage of desmosomal proteins results in the disruption of the structure of desmosomes and contributes to cell rounding and disassembly of the intermediate filament network (Weiske et al., 2001). The cytosolic fragment has implications for the autoimmune disease, Pemphigus vulgaris (Tong et al. 2006).
REACT_12404 (Reactome) Caspase-3 cleaves DFF45 between residues 224,225.
REACT_12450 (Reactome) Acinus induces apoptotic chromatin condensation after cleavage and activation by CASP3 (Sahara et al., 1999).
REACT_12471 (Reactome) Caspase mediated cleavage produces a constitutively active kinase that induces apoptosis (Ghayur et al.,1996).
REACT_12531 (Reactome) Caspase-3-mediated cleavage of ROCK I induces MLC phosphorylation and apoptotic membrane blebbing (Sebbagh et al., 2001). Cleavage and activation of ROCK-1 by caspase-3 plays has also been shown to play a crucial role in in cardiac myocyte apoptosis (Chang et al., 2006).
REACT_12544 (Reactome) Caspase-3 cleaves the DFF45 subunit of the DFF45:DFF40 complex at two sites to generate an active DNA fragmentation factor. One site of cleavage is between residues 117,118 (Liu et al., 1997) .
REACT_12638 (Reactome) Cleavage of PKCtheta by Caspase-3 induces nuclear fragmentation and lethality (Datta et al., 1997)
REACT_13406 (Reactome) Proteolytic cleavage of the COOH-terminal domain of Mst3 by caspases promotes nuclear translocation of the catalytic domain (Huang et al., 2002).
REACT_13409 (Reactome) The subcellular localization of PAK-2 is controlled by nuclear localization and nuclear export signal motifs (Jakobi et al.,2003). The regulatory domain contains a nuclear export signal motif that prevents the nuclear accumulation of full-length PAK-2. The activating proteolytic cleavage disrupts the nuclear export signal in PAK-2 and removes most its regulatory domain. The resulting activated PAK-2p34 fragment contains a nuclear localization signal and translocates to and is retained in the nucleus (Jakobi et al.,2003).
REACT_13414 (Reactome) Caspase-3 cleaves Tau at position 421 in vitro producing an N-terminal fragment that functions as an apoptotic effector (Fasulo et al., 2000).
REACT_13417 (Reactome) Cleavage of Etk by caspase-3 stimulates its kinase activity. Overexpression of the fragment induces apoptosis (Wu et al.,2001).
REACT_13418 (Reactome) Desmosomes represent one of the anchoring junctions mediating strong cell-cell contacts.Desmosomal plaque proteins including the head domain of plakophilin provide interaction sites for cytokeratin filaments (see references in Weiske et al.,2001). Proteolytic fragmentation of these proteins prevents binding of intermediate filaments and in consequence results in remodeling of the intermediate filament cytoskeleton (Weiske et al., 2001).Cleaved Plakophilin-1 appears to be is impaired in supporting the formation and maintenance of desmosomes during apoptosis (Weiske et al., 2001).
REACT_13428 (Reactome) Vimentin is cleaved by several caspases during apoptosis (Morishima et al., 1999, Byun et al., 2001). This cleavage disrupts the cytoplasmic network of intermediate filaments and coincides temporally with nuclear fragmentation. Caspase-6 recognizes and cleaves C terminal side of Asp-429. Vimentin is cleaved at Asp85 by caspases-3 and -7 (Byun et al., 2001). This clevage generates a pro-apoptotic amino-terminal cleavage product (amino acids 1-85) that amplifies the cell death signal (Byun et al., 2001).
REACT_13431 (Reactome) Inactive PAK-2 can be partially autophosphorylated in the regulatory region without being activated (Gatti et al. 1999).
REACT_13468 (Reactome) Caspase-mediated cleavage of Mst3 activates its intrinsic kinase activity. Proteolytic removal of the COOH-terminal domain promotes nuclear translocation of its kinase domain. Ectopic expression of COOH-terminal truncated Mst3 results in DNA fragmentation and morphological changes characteristic of apoptosis (Huang et al., 2002).
REACT_13476 (Reactome) Caspases initiate the destruction of the nucleus cleavage of lamins leads to
disassembly of the nuclear lamina. Lamin A is cleaved by active caspase 6 (Orth et al., 1996).
REACT_13484 (Reactome) Caspases initiate the destruction of the nucleus cleavage of lamins leads to  disassembly of the nuclear lamina. Lamin B is cleaved by active caspase 6 (Orth et al., 1996) (Rao et al., 1996).
REACT_13489 (Reactome) Vimentin is cleaved by several caspases during apoptosis (Morishima et al., 1999, Byun et al., 2001). This clevage disrupts the cytoplasmic network of intermediate filaments and coincides temporally with nuclear fragmentation. Asp259 is recognized and cleaved by caspase-6 (Byun et al., 2001).
REACT_13508 (Reactome) Active caspase-3 is translocated from the cytoplasm to the nucleus during progression through apoptosis (Kamada et al., 2005).
REACT_13513 (Reactome) The major HMG-box-containing chromatin proteins HMGB1 and HMGB2 stimulate DNA cleavage by DFF40/CAD (Liu et al., 1998; Toh et al., 1998; Widlak et al., 2000). Changes in DNA conformation following HMG-box binding makes the substrate more accessible to cleavage by DFF40/CAD nuclease and thus may contribute to preferential linker DNA cleavage during apoptosis (Kalinowska-Herok and Widlak., 2008).
REACT_13514 (Reactome) Direct interactions between the histone H1 C-terminal domain and DFF40/CAD possibly target the nuclease to chromatin linker DNA promoting the linker DNA cleavage during the terminal stages of apoptosis (Widlak et al., 2005). Noteworthy, it has been reported that DFF40/DFF45 complexes could also associate with chromatin and be activated with caspase-3 in DNA-bound state (Korn et al., 2005).
REACT_13519 (Reactome) Vimentin is cleaved by several caspases during apoptosis (Morishima et al., 1999, Byun et al., 2001). This clevage disrupts the cytoplasmic network of intermediate filaments and coincides temporally with nuclear fragmentation. Caspase-6 recognizes and cleaves C terminal side of Asp-429.
REACT_13522 (Reactome) Plectin is a major cross-linking protein of the three main cytoplasmic filament systems. Caspase-8 mediated cleavage of plectin 1 appears to contribute to disruption of the microfilament system during the early stages of apoptosis (Stegh et al., 2000).
REACT_13544 (Reactome) DFF associated with alpha-importin:beta-importin is translocated to the nucleus (Neimanis et al., 2007)
REACT_13549 (Reactome) Following iinduction of apoptosis in epithelial cells, tight junction are disrupted. Tight junction proteins, including the the transmembrane protein occludin and the cytoplasmic adaptor proteins ZO-1 and ZO-2 are fragmented by caspase cleavage (Bojarski et al., 2004).
REACT_13554 (Reactome) Caspase-8 mediated cleavage of BAP31 at the ER produces a pro-apoptotic p20 fragment that remains at the ER (Breckenridgeet al., 2003). Cleavage stimulates Ca2+-dependent mitochondrial fission, enhancing the release of cytochrome C (Breckenridgeet al., 2003).
REACT_13560 (Reactome) Adenoviral expression of the BAP31 cleavage product, p20 causes early release of Ca2+ from the ER, concomitant uptake of Ca2+ into mitochondria, and recruitment of Drp1 to the mitochondria (Breckenridge et al., 2003) . Drp1 mediates scission of the outer mitochondrial membrane, resulting in dramatic fragmentation and fission of the mitochondrial network .
REACT_13587 (Reactome) Cleavage of the C-terminal cytoplasmic domain of occludin during apoptosis generates a fragment that can longer associate with the cytoplasmic adapter proteins ZO-1, -2 and -3 and, as a consequence, with the actin cytoskeleton (Bojarski et al., 2003) . Cleavage of ZO-1 and ZO-2 further disrupts tight junction structure and function . Notably, claudins, which are associated with ZO-1, ZO-2 and ZO-3, completely lose their linkage to the actin cytoskeleton and other ZO-1-, ZO-2-, ZO-3-interacting proteins.(Bojarski et al., 2003) .
REACT_13598 (Reactome) In apoptotic cells, intercellular contacts are disrupted through the activity of caspases. Apoptotic cleavage of Dsg2,the most widespread desmosomal cadherin, is mediated by caspase 3 in epithelial cells (Cirillo et al., 2008).
REACT_13605 (Reactome) Cleavage of desmosomal proteins including desmoplakin contributes to cell rounding and disintegration of the intermediate filament system (Weiske et al., 2001).
REACT_13636 (Reactome) MASK is cleaved in vitro by caspase 3 . C-terminally truncated forms of MASK can both induce apoptosis upon overexpression in mammalian cells (Dan et al., 2002).
REACT_13652 (Reactome) Claspin is cleaved by caspase-7 during the initiation of apoptosis following DNA damage (Clarke et al., 2005). Claspin is cleaved at a single aspartate residue into a large N-terminal fragment and a smaller C-terminal fragment that contain different functional domains. Only the large N-terminal fragment retains Chk1 binding activity. The smaller C-terminal fragment associates with DNA and inhibits the DNA-dependent phosphorylation of Chk1 associated with its activation indicating that cleavage of Claspin by caspase-7 inactivates the Chk1 signaling pathway (Clarke et al., 2005).
REACT_13679 (Reactome) DNA Fragmentation Factor (DFF), is a heterodimer of 40 kDa (DFF40) and 45 kDa (DFF45) subunits (Liu et al., 1997). DFF45 (ICAD) appears to act as a chaperone for DFF40 (CAD) during its synthesis, remaining complexed with it to inhibit its DNase activity (Enari et al., 1998). The complex could exist as: a DFF40:DFF45 heterodimer, a (DFF40:DFF45)2 heterotetramer or a (DFF40:DFF40:DFF45:DFF45) heterotetramer (Lechardeur et al., 2005).
REACT_13689 (Reactome) Following caspase-3 cleavage, the fragments of DFF45 dissociate from DFF40, the active component of DFF (Liu et al. 1998).
REACT_13702 (Reactome) The DFF40 cleaves DNA substrates to generate fragments possessing ends with 5’-phosphate and 3’-hydroxyl groups, and generates exclusively double strand breaks (primarily blunt ends). It has some sequence preferences on naked DNA substrates and prefers purine/pyrimidine blocks with rotational symmetry (Widlak et al., 2000). DFF is both a deoxyribonucleotide-specific and a double-strand-specific endonuclease (Hanus et al., 2008).
REACT_13708 (Reactome) Following its release from DFF45, DFF40 forms homodimers, which are the basic structures of the enzymatically active nuclease (Woo et al., 2004). Following dimerization, DFF40 can further oligomerize forming units containing at least 4 monomers (Liu et al., 1999; Widlak et al., 2003).
REACT_13713 (Reactome) Active caspase 8 associates with the membranes during apoptosis caused by multiple stimuli (Chandra et al., 2004). OMM-localized active caspase 8 can activate cytosolic caspase 3 and ER-localized BAP31 (Chandra et al., 2004) .
REACT_13747 (Reactome) p21-activated protein kinase (PAK-2), also known as gamma-PAK, is cleaved by caspase-3 during apoptosis and plays a role in regulating cell death. Cleavage produces two peptides; 1-212 containing most of the regulatory domain and 213-524 containing 34 amino acids of the regulatory domain as well as the catalytic domain (Walter et al., 1998). Proteolytic cleavage of PAK by caspase-3 creates the constitutively active PAK-2p34 fragment (Jakobi et al., 2003). Evidence for this reaction comes from experiments using both human and rabbit proteins.
REACT_13756 (Reactome) The translocation of the DFF complex from the cytoplasm to the nucleus is mediated by the importin alfa/beta heterodimer. Both DFF40 and DFF45 possess NLS at their C-termini that interact directly with the importin alfa/beta heterodimer. However, DFF complex binds more tightly compared with the individual subunits and C-termini of both subunits are required for DFF nuclear import (Neimanis et al., 2007).
REACT_13795 (Reactome) Gelsolin is cleaved by caspase-3 generating a constitutively
active fragment that can depolymerize F-actin contributing to actin cytoskeletal collapse (Kothakota et al., 1997)
REACT_13813 (Reactome) Cleavage of the C-terminal cytoplasmic domain of occludin during apoptosis generates a fragment that can longer associate with the cytoplasmic adapter proteins ZO-1, -2 and -3 and, as a consequence, with the actin cytoskeleton (Bojarski et al., 2003) . Cleavage of ZO-1 and ZO-2 further disrupts tight junction structure and function . Notably, claudins, which are associated with ZO-1, ZO-2 and ZO-3, completely lose their linkage to the actin cytoskeleton and other ZO-1-, ZO-2-, ZO-3-interacting proteins.(Bojarski et al., 2003) .
REACT_13820 (Reactome) Activation of PAK-2p34 coincides with autophosphorylation of Thr 402 in the the catalytic domain (Walter et al., 1998).
REACT_22225 (Reactome) Cleaved Satb1 dissociates from chromatin and may function in high molecular weight DNA fragmentation (Galande et al., 2001).
ROCK1(1-1113)ArrowREACT_12531 (Reactome)
ROCK1(1-1354)REACT_12531 (Reactome)
ROCK1(1114-1354)ArrowREACT_12531 (Reactome)
SATB1(1-254)ArrowREACT_22225 (Reactome)
SATB1(255-763)ArrowREACT_22225 (Reactome)
SATB1REACT_22225 (Reactome)
SPTAN1(1-1185)ArrowREACT_12024 (Reactome)
SPTAN1(1186-2472)ArrowREACT_12024 (Reactome)
SPTAN1REACT_12024 (Reactome)
STK24(1-313)ArrowREACT_13406 (Reactome)
STK24(1-313)ArrowREACT_13468 (Reactome)
STK24(1-313)REACT_13406 (Reactome)
STK24(1-443)REACT_13468 (Reactome)
STK24(314-443)ArrowREACT_13468 (Reactome)
TJP1ArrowREACT_13587 (Reactome)
TJP1REACT_13587 (Reactome)
TJP2(?-?)ArrowREACT_13813 (Reactome)
TJP2REACT_13813 (Reactome)
VIM(2-259)ArrowREACT_13489 (Reactome)
VIM(2-429)ArrowREACT_13519 (Reactome)
VIM(2-85)ArrowREACT_13428 (Reactome)
VIM(260-466)ArrowREACT_13489 (Reactome)
VIM(430-466)ArrowREACT_13519 (Reactome)
VIM(86-466)ArrowREACT_13428 (Reactome)
VIMREACT_13428 (Reactome)
VIMREACT_13489 (Reactome)
VIMREACT_13519 (Reactome)
active caspase 3mim-catalysisREACT_11997 (Reactome)
active caspase 3mim-catalysisREACT_12072 (Reactome)
active caspase 3mim-catalysisREACT_12082 (Reactome)
active caspase 3mim-catalysisREACT_13598 (Reactome)
active caspase-3ArrowREACT_13508 (Reactome)
active caspase-3REACT_13508 (Reactome)
active caspase-3mim-catalysisREACT_12012 (Reactome)
active caspase-3mim-catalysisREACT_12014 (Reactome)
active caspase-3mim-catalysisREACT_12022 (Reactome)
active caspase-3mim-catalysisREACT_12024 (Reactome)
active caspase-3mim-catalysisREACT_12025 (Reactome)
active caspase-3mim-catalysisREACT_12044 (Reactome)
active caspase-3mim-catalysisREACT_12045 (Reactome)
active caspase-3mim-catalysisREACT_12404 (Reactome)
active caspase-3mim-catalysisREACT_12450 (Reactome)
active caspase-3mim-catalysisREACT_12471 (Reactome)
active caspase-3mim-catalysisREACT_12531 (Reactome)
active caspase-3mim-catalysisREACT_12544 (Reactome)
active caspase-3mim-catalysisREACT_12638 (Reactome)
active caspase-3mim-catalysisREACT_13414 (Reactome)
active caspase-3mim-catalysisREACT_13417 (Reactome)
active caspase-3mim-catalysisREACT_13636 (Reactome)
active caspase-3mim-catalysisREACT_13747 (Reactome)
active caspase-3mim-catalysisREACT_13795 (Reactome)
active caspase-6mim-catalysisREACT_13476 (Reactome)
active caspase-6mim-catalysisREACT_13484 (Reactome)
active caspase-6mim-catalysisREACT_13519 (Reactome)
active caspase-6mim-catalysisREACT_22225 (Reactome)
active caspase-7mim-catalysisREACT_12021 (Reactome)
active caspase-7mim-catalysisREACT_13652 (Reactome)
active caspase-8ArrowREACT_13713 (Reactome)
active caspase-8REACT_13713 (Reactome)
active caspase-8mim-catalysisREACT_13489 (Reactome)
active caspase-8mim-catalysisREACT_13522 (Reactome)
active caspase-8mim-catalysisREACT_13554 (Reactome)
beta-cateninREACT_12022 (Reactome)
caspase 3/caspase 7mim-catalysisREACT_12004 (Reactome)
caspase 3/caspase 7mim-catalysisREACT_13428 (Reactome)
caspase-3-cleaved

DFF45 (117,224):DFF40

complex
ArrowREACT_12404 (Reactome)
caspase-3-cleaved

DFF45 (117,224):DFF40

complex
REACT_13689 (Reactome)
importin-alpha:importin-betaREACT_13756 (Reactome)
p-5S-PAK2(1-212)ArrowREACT_13747 (Reactome)
p-5S-PAK2(1-524)ArrowREACT_13431 (Reactome)
p-5S-PAK2(1-524)REACT_13747 (Reactome)
p-T402-PAK2(1-524)ArrowREACT_13409 (Reactome)
p-T402-PAK2(213-524)ArrowREACT_13820 (Reactome)
p-T402-PAK2(213-524)REACT_13409 (Reactome)
unidentified caspase

acting on

Desmoplakin
mim-catalysisREACT_13605 (Reactome)
unidentified caspase

acting on

Plakophilin 1
mim-catalysisREACT_13418 (Reactome)
unidentified caspase acting on Occludinmim-catalysisREACT_13549 (Reactome)
unidentified caspase acting on ZO-1mim-catalysisREACT_13587 (Reactome)
unidentified caspase acting on ZO-2mim-catalysisREACT_13813 (Reactome)
unidentified caspasemim-catalysisREACT_13468 (Reactome)
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