Apoptotic execution phase (Homo sapiens)

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50392, 3486492952193833212745, 46513222391831121513, 14348, 928384, 5111716113824-26740-423835192236103743, 4420332322473019endoplasmic reticulum membranecytosolnucleoplasmmitochondrial matrixHistone H1 bound chromatin DNADrp1Caspase-8 dimerBAP31GAS2 (1-279)active caspase-6active caspase-7Alpha adducin fragment (1-633)DFF45 fragment (1-117)caspase 3/caspase 7Desmoglein 3 fragment (782-999)Claspinspectrin alpha chain, brain/alpha II fodrinClaspin fragment(1073-1332)active caspase-7farnesyltransferase/geranyl-geranyltransferase subunit alphaGelsolin (27-403 fragment)DFF40/DFFB/CADFADK 1 fragment (773-1052)HMGB1/HMGB2MASK fragment (1-305)Alpha adducin fragment (634-737)Rock1 fragment (1-1113)Caspase-cleaved ZO-1 fragmentsAcinusGAS2ADPBAP31 fragment (2-164)Caspase cleaved DFF45 (117)Plectin 1BAP31 fragment (165-237)MST3proteolytically cleaved ZO-2DFF45:DFF40 complexEtk fragment (1-242)unidentified caspase acting on Plakophilin 1Epithelial-cadherin precursor fragment (155-750)Lamin A fragment (1-230)Lamin B1 (fragment 1-231)proteolytically cleaved Plakophilin 1vimentin (260-466 fragment)APCRock1 fragment (1114-1354)vimentin (86-466 fragment)BAP31 fragment (238-246)Protein kinase C, theta type fragment (1-354)PKC-delta fragment (330-676)active caspase-3Satb1 (fragment (1-254)DFF:associated with the importin-alpha:importin-beta complexHIP-55Gelsolinunidentified caspase acting on ZO-1Satb1PAK2MST3 fragment (1-313)spectrin alpha chain/alpha-II-Fodrin fragment (1-1185)proteolytically cleaved DesmoplakinLamin A (fragment 231-664)Desmoplakinactive caspase-6PAK-2p34unidentified caspase acting on DesmoplakinADPOccludinATPDesmoglein 2beta-catenin-1(1-115)Caspase-8 dimerPlectin 1 fragment (1-2395)DFF45:DFF40 complexLamin B1 fragment (232-586)DNADFF40/DFFB/CADDFF40 homodimer/homooligomerAPC fragment (778-2843)active caspase-3Occludin fragment (1-320)Protein kinase C, theta typeOccludin fragment (321-522)DFF:associated with the importin-alpha:importin-beta complexC-IAP1(373-618 )HIP-55 fragment (362-431)EtkDFFA/DFF1/DFF45APC fragment (1-777)Acinus fragment (1-1093)DFF40 associated with chromatinDesmoglein 1 fragment (889-1049)Desmoglein 1importin-alpha:importin-betaHMGB1/HMGB2- bound chromatinpartially autophosphorylated full length PAK-2 (inactive)ATPphospho-PAK-2p34 (Thr 402)vimentin (2-429 fragment)DFF45 fragment (118-224)Acinus fragment (1094-1341)DFF cleaved DNAMST3 fragment (1-313)Adducin alphaClaspin fragment (1-1072)vimentin (2-259 fragment)Drp1Plakophilin 1Tau fragment (2-421)FADK1ZO-1unidentified caspase acting on ZO-2Rock1unidentified caspaseHIP-55 fragment (1-361)Lamin AC-IAP1(1-372)Desmoglein 3 fragment (50-781)farnesyltransferase/geranyl-geranyltransferase subunit alpha fragment (60-379)c-IAP1beta-cateninGelsolin (404-782 fragment)Desmoglein 1 fragment (50-888)Desmoglein 3TauMASKSatb1 (fragment (255-763)Cadherin-1Etk fragment (243-675)vimentin (430-466 fragment)active caspase 3Epithelial-cadherin precursor fragment (751-882)vimentin (2-85 fragment)beta-catenin-1(116-376)spectrin alpha chain/alpha-II-Fodrin fragment (1186-2472)Protein kinase C, theta type fragment (355-706)caspase-3-cleaved DFF45 (117,224):DFF40 complexPlectin 1 fragment (2396-4684)PKC-delta (fragment 1-329)DFF45 fragment (225-331)Lamin B1Tau fragment (422-758)Desmoglein 2 (70 Kd fragment)partially auto-phosphorylated PAK-2 fragment (1-212)FADK 1 fragment (1-772)MST3 fragment (314-443)ZO-2DFF40 homodimerMASK fragment (306-416)phospho-PAK-2p34 (Thr 402)GAS2 (280-313)unidentified caspase acting on OccludinPKC-deltafarnesyltransferase/geranyl-geranyltransferase subunit alpha fragment (1-59)vimentin (2-466 fragment)4, 52, 31


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).

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Bibliography

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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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  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
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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
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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
  58. Ghayur T, Hugunin M, Talanian RV, Ratnofsky S, Quinlan C, Emoto Y, Pandey P, Datta R, Huang Y, Kharbanda S, Allen H, Kamen R, Wong W, Kufe D.; ''Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis.''; PubMed Europe PMC Scholia
  59. Turowec JP, Zukowski SA, Knight JD, Smalley DM, Graves LM, Johnson GL, Li SS, Lajoie GA, Litchfield DW.; ''An unbiased proteomic screen reveals caspase cleavage is positively and negatively regulated by substrate phosphorylation.''; PubMed Europe PMC Scholia

History

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114845view16:34, 25 January 2021ReactomeTeamReactome version 75
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100035view16:24, 31 October 2018ReactomeTeamreactome version 63
99588view14:58, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
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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
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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
ADP Metabolite16761 (ChEBI)
APC ProteinREACT_10434 (Reactome)
APC fragment (1-

777)

ProteinREACT_12313 (Reactome)
APC fragment (778-

2843)

ProteinREACT_12296 (Reactome)
ATP Metabolite15422 (ChEBI)
Acinus ProteinQ9UKV3 (UniProt)
Acinus fragment

(1094-1341)

ProteinQ9UKV3 (UniProt)
Acinus fragment (1-

1093)

ProteinQ9UKV3 (UniProt)
Adducin alpha ProteinP35611 (UniProt)
Alpha adducin

fragment (634-737)

ProteinP35611 (UniProt)
Alpha adducin

fragment (1-633)

ProteinP35611 (UniProt)
BAP31 ProteinP51572 (UniProt)
BAP31 fragment

(165-237)

ProteinP51572 (UniProt)
BAP31 fragment

(2-164)

ProteinP51572 (UniProt)
BAP31 fragment

(238-246)

ProteinP51572 (UniProt)
C-IAP1(1-372) ProteinQ13490 (UniProt)
C-IAP1(373-618 ) ProteinQ13490 (UniProt)
Cadherin-1 ProteinP12830 (UniProt)
Caspase cleaved

DFF45 (117)

ComplexREACT_13101 (Reactome)
Caspase-8 dimer ComplexREACT_13946 (Reactome)
Caspase-8 dimer ComplexREACT_4185 (Reactome)
Caspase-cleaved

ZO-1 fragments

ProteinQ07157-1 (UniProt)
Claspin ProteinQ9HAW4 (UniProt)
Claspin fragment

(1073-1332)

ProteinQ9HAW4 (UniProt)
Claspin fragment (1-

1072)

ProteinQ9HAW4 (UniProt)
DFF cleaved DNA ComplexREACT_14657 (Reactome)
DFF40

homodimer/homoolig omer

UnknownREACT_14397 (Reactome)
DFF40 associated

with chromatin

ComplexREACT_14402 (Reactome)
DFF40 homodimer ComplexREACT_14622 (Reactome)
DFF40/DFFB/CAD ProteinO76075 (UniProt)
DFF45 fragment

(118-224)

ProteinO00273 (UniProt)
DFF45 fragment

(225-331)

ProteinO00273 (UniProt)
DFF45 fragment (1-

117)

ProteinO00273 (UniProt)
DFF45:DFF40

complex

ComplexREACT_12695 (Reactome)
DFF45:DFF40

complex

ComplexREACT_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/DFF1/DFF45 ProteinO00273 (UniProt)
DNA UnknownREACT_3913 (Reactome)
Desmoglein 1 ProteinQ02413 (UniProt)
Desmoglein 1

fragment (50-888)

ProteinQ02413 (UniProt)
Desmoglein 1

fragment (889-1049)

ProteinQ02413 (UniProt)
Desmoglein 2 ProteinQ14126 (UniProt)
Desmoglein 2 (70

Kd fragment)

ProteinQ14126 (UniProt) 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)
Desmoglein 3 ProteinP32926 (UniProt)
Desmoglein 3

fragment (782-999)

ProteinP32926 (UniProt)
Desmoglein 3

fragment (50-781)

ProteinP32926 (UniProt)
Desmoplakin ProteinP15924 (UniProt)
Drp1 ProteinO00429 (UniProt)
Epithelial-cadherin

precursor fragment (155-750)

ProteinP12830 (UniProt)
Epithelial-cadherin

precursor fragment (751-882)

ProteinP12830 (UniProt)
Etk ProteinP51813 (UniProt)
Etk fragment (1-242) ProteinP51813 (UniProt)
Etk fragment (243-

675)

ProteinP51813 (UniProt)
FADK 1 fragment

(773-1052)

ProteinQ05397 (UniProt)
FADK 1 fragment (1-

772)

ProteinQ05397 (UniProt)
FADK1 ProteinQ05397 (UniProt)
GAS2 ProteinO43903 (UniProt)
GAS2 (1-279) ProteinO43903 (UniProt)
GAS2 (280-313) ProteinO43903 (UniProt)
Gelsolin ProteinP06396 (UniProt)
Gelsolin (27-403

fragment)

ProteinP06396 (UniProt)
Gelsolin (404-782

fragment)

ProteinP06396 (UniProt)
HIP-55 ProteinQ9UJU6 (UniProt)
HIP-55 fragment

(1-361)

ProteinQ9UJU6 (UniProt)
HIP-55 fragment

(362-431)

ProteinQ9UJU6 (UniProt)
HMGB1/HMGB2 ProteinREACT_14288 (Reactome)
HMGB1/HMGB2-

bound chromatin

ComplexREACT_14370 (Reactome)
Histone H1 bound

chromatin DNA

ComplexREACT_14129 (Reactome)
Lamin A ProteinP02545-1 (UniProt)
Lamin A (fragment

231-664)

ProteinP02545-1 (UniProt)
Lamin A fragment (1-

230)

ProteinP02545-1 (UniProt)
Lamin B1 ProteinP20700 (UniProt)
Lamin B1 (fragment

1-231)

ProteinP20700 (UniProt)
Lamin B1 fragment

(232-586)

ProteinP20700 (UniProt)
MASK ProteinQ9P289 (UniProt)
MASK fragment (1-305) ProteinQ9P289 (UniProt)
MASK fragment (306-

416)

ProteinQ9P289 (UniProt)
MST3 ProteinQ9Y6E0 (UniProt)
MST3

fragment (1-313)

ProteinQ9Y6E0 (UniProt)
MST3 fragment (1-

313)

ProteinQ9Y6E0 (UniProt)
MST3 fragment (314-

443)

ProteinQ9Y6E0 (UniProt)
Occludin ProteinQ16625 (UniProt)
Occludin fragment

(1-320)

ProteinQ16625 (UniProt)
Occludin fragment

(321-522)

ProteinQ16625 (UniProt)
PAK-2p34 ProteinQ13177 (UniProt)
PAK2 ProteinQ13177 (UniProt)
PKC-delta ProteinQ05655 (UniProt)
PKC-delta fragment

(330-676)

ProteinQ05655 (UniProt)
PKC-delta (fragment

1-329)

ProteinQ05655 (UniProt)
Plakophilin 1 ProteinQ13835 (UniProt)
Plectin 1 ProteinQ15149 (UniProt)
Plectin 1 fragment

(2396-4684)

ProteinQ15149 (UniProt)
Plectin 1 fragment (1-

2395)

ProteinQ15149 (UniProt)
Protein kinase C,

theta type

ProteinQ04759 (UniProt)
Protein kinase C,

theta type fragment (1-354)

ProteinQ04759 (UniProt)
Protein kinase C,

theta type fragment (355-706)

ProteinQ04759 (UniProt)
Rock1 ProteinQ13464 (UniProt)
Rock1 fragment

(1114-1354)

ProteinQ13464 (UniProt)
Rock1 fragment (1-

1113)

ProteinQ13464 (UniProt)
Satb1 ProteinQ01826 (UniProt)
Satb1 (fragment

(1-254)

ProteinQ01826 (UniProt)
Satb1 (fragment

(255-763)

ProteinQ01826 (UniProt)
Tau ProteinP10636 (UniProt)
Tau fragment (2-

421)

ProteinP10636 (UniProt)
Tau fragment (422-

758)

ProteinP10636 (UniProt)
ZO-1 ProteinQ07157-1 (UniProt)
ZO-2 ProteinQ9UDY2 (UniProt)
active caspase 3 ComplexREACT_12262 (Reactome)
active caspase-3 ComplexREACT_13159 (Reactome)
active caspase-3 ComplexREACT_2467 (Reactome)
active caspase-6 ComplexREACT_14257 (Reactome)
active caspase-6 ComplexREACT_14343 (Reactome)
active caspase-7 ComplexREACT_14263 (Reactome)
active caspase-7 ComplexREACT_3366 (Reactome)
beta-catenin ProteinREACT_10304 (Reactome)
beta-catenin-1(1-

115)

ProteinP35222-1 (UniProt)
beta-catenin-1(116-

376)

ProteinP35222-1 (UniProt)
c-IAP1 ProteinQ13490 (UniProt)
caspase 3/caspase 7 UnknownREACT_12368 (Reactome)
caspase-3-cleaved

DFF45 (117,224): DFF40 complex

ComplexREACT_13244 (Reactome)
farnesyltransferase/g

eranyl- geranyltransferase subunit alpha

ProteinP49354 (UniProt)
farnesyltransferase/g

eranyl- geranyltransferase subunit alpha fragment (1-59)

ProteinP49354 (UniProt)
farnesyltransferase/g

eranyl- geranyltransferase subunit alpha fragment (60-379)

ProteinP49354 (UniProt)
importin-alpha:

importin-beta

ComplexREACT_13986 (Reactome)
partially

autophosphorylated full length PAK-2 (inactive)

ProteinQ13177 (UniProt)
partially auto-

phosphorylated PAK-2 fragment (1-212)

ProteinQ13177 (UniProt)
phospho-PAK-2p34

(Thr 402)

ProteinQ13177 (UniProt)
proteolytically

cleaved Desmoplakin

ProteinP15924 (UniProt)
proteolytically

cleaved Plakophilin 1

ProteinQ13835 (UniProt)
proteolytically

cleaved ZO-2

ProteinQ9UDY2 (UniProt)
spectrin alpha

chain/alpha-II-Fodrin fragment (1-1185)

ProteinQ13813 (UniProt)
spectrin alpha

chain/alpha-II-Fodrin fragment (1186- 2472)

ProteinQ13813 (UniProt)
spectrin alpha chain,

brain/alpha II fodrin

ProteinQ13813 (UniProt)
unidentified caspase UnknownREACT_14138 (Reactome)
unidentified caspase

acting on Desmoplakin

UnknownREACT_21697 (Reactome)
unidentified caspase

acting on Occludin

UnknownREACT_21584 (Reactome)
unidentified caspase

acting on Plakophilin 1

UnknownREACT_21872 (Reactome)
unidentified caspase

acting on ZO-1

UnknownREACT_22050 (Reactome)
unidentified caspase

acting on ZO-2

UnknownREACT_22003 (Reactome)
vimentin (2-259

fragment)

ProteinP08670 (UniProt)
vimentin (2-429

fragment)

ProteinP08670 (UniProt)
vimentin (2-466

fragment)

ProteinP08670 (UniProt)
vimentin (2-85

fragment)

ProteinP08670 (UniProt)
vimentin (260-466

fragment)

ProteinP08670 (UniProt)
vimentin (430-466

fragment)

ProteinP08670 (UniProt)
vimentin (86-466

fragment)

ProteinP08670 (UniProt)

Annotated Interactions

No annotated interactions

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