Apoptotic execution phase (Homo sapiens)

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39275434153519, 3718, 2451471511, 16143338, 5935655, 5726451598341329342834237, 20, 323121, 4150524628493, 4, 37384358531250153540481028134222, 30cytosolnucleoplasmmitochondrial matrixendoplasmic reticulum membraneCASP8(217-374) SATB1(1-254)DSG2HIST1H1C DFFA(225-331)DFFA BIRC2(373-618)SPTAN1(1186-2472)HIST1H1B Histone H1 boundchromatin DNAPRKCQDFFA(1-117)HIST1H1E GSN(404-782)DNA GAS2KPNA1 CASP7(24-198) importin-alpha:importin-beta complexFNTA(59-379)HMGB1/HMGB2- boundchromatinCDH1(155-882)CTNNB1(1-115)CASP8(217-374) BCAP31(238-246)HIST1H1D DFFA(1-?) p-5S-PAK2(2-212)PRKCD(330-676)DFFA(1-?) TJP2BIRC2HMGB1 PRKCD(1-329)DFFA(225-331) CTNNB1 SPTAN1(1-1185)DNA DFFADBNL(1-361)active caspase-8VIM(2-85)HIST1H1E PKP1(?-?)Caspase-3, Caspase-7H1F0 ADPp-5S-PAK2MAPT(422-758)DFFA(118-224) CASP3(176-277) LMNB1HMGB1 SATB1(255-763)PLECCaspase-7p-T402-PAK2(213-524)DFFB LMNB1(232-586)HIST1H1C DFFA(118-331) VIM(260-466)HIST1H1A DSG3CASP3(29-175) CASP7(24-198) DFFA DNM1LVIM(86-466)ATPactive caspase-7KPNB1 HMGB2 HIST1H1B DSG1(50-888)SATB1importin-alpha:importin-betaAPCCLSPN(1073-1332)BIRC2(1-372)DSG2(?-1118)HIST1H1B ADD1H1F0 PAK2(213-524)beta-cateninDFFB APC(778-2843)DFFB DFFBMST4KPNB1 p-T402-PAK2(213-524)Caspase-3STK24DFF40 homooligomer BMXPTK2(1-772)PRKCQ(1-354)DFFB PTK2(773-1052)DFFB LMNA(1-230)DFFB Caspase cleaved DFFA(117)KPNB1 DFF40 homooligomer active caspase-8FNTA(2-379)TJP1PAK2Lamin AOCLNSPTAN1DNA PLEC(1-2395)FNTA(1-59)DFFB PTK2BMX(243-675)DFFA(1-117) BCAP31(165-237)STK24(1-313)LMNA(231-664)KPNA1 LMNB1(1-231)PLEC(2396-4684)TJP1 (?-?)VIM(2-259)DBNL(362-431)GSNDFF40homodimer/homooligomerSTK24(314-443)CASP7(207-303) GSN(28-403)TJP2(?-?)CASP7(207-303) DFFB CASP8(385-479) CLSPN(1-1072)DFFA:DFFBH1F0 KPNA1 MST4(306-416)DFF:associatedwiththeimportin-alpha:importin-beta complexactive caspase-6CASP7(24-198) CLSPNADD1(634-737)ROCK1DNM1LDSP(?-?)KPNA1 VIM(2-429)HIST1H1A GAS2(1-279)DFF40 homodimerDSG3(50-781)DFF:associatedwiththeimportin-alpha:importin-beta complexHMGB1/HMGB2MAPT(2-421)DFFA:DFFBBCAP31(2-164)HMGB2 PKP1active caspase-6HIST1H1D ACIN1(1094-1341)VIMCASP3(176-277) CASP8(385-479) HIST1H1A PRKCDOCLN(321-522)ACIN1DFF cleaved DNA fragments MAPTBCAP31(2-245)MST4(1-305)STK24(1-313)APC(1-777)VIM(430-466)BMX(1-242)DFFBCTNNB1(116-376)DSG1ATPKPNB1 DFFB CASP6(194-293) HIST1H1D HIST1H1C DSG1(889-1049)DSPDFF cleaved DNADFFA(118-224)GAS2(280-313)DFF40 associatedwith chromatinCDH1(155-750)CASP6(24-179) DBNLPRKCQ(355-706)HIST1H1E CASP7(207-303) CASP3(29-175) DSG3(782-999)active caspase-3ADPCASP3(176-277) CASP3(29-175) ACIN1(1-1093)ROCK1(1-1113)DNADFFA(1-117) ROCK1(1114-1354)OCLN(1-320)CDH1(751-882)ADD1(1-633)caspase-3-cleavedDFFA (117,224):DFFBcomplexCASP6(24-179) CASP6(194-293) 24417, 5611, 1625, 3644442, 25, 3618, 244417, 564444


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). View original pathway at Reactome.


Pathway is converted from Reactome ID: 75153
Reactome version: 75
Reactome Author 
Reactome Author: Alnemri, E

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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
  3. Woo EJ, Kim YG, Kim MS, Han WD, Shin S, Robinson H, Park SY, Oh BH.; ''Structural mechanism for inactivation and activation of CAD/DFF40 in the apoptotic pathway.''; PubMed Europe PMC Scholia
  4. Widlak P, Lanuszewska J, Cary RB, Garrard WT.; ''Subunit structures and stoichiometries of human DNA fragmentation factor proteins before and after induction of apoptosis.''; PubMed Europe PMC Scholia
  5. Fasulo L, Ugolini G, Visintin M, Bradbury A, Brancolini C, Verzillo V, Novak M, Cattaneo A.; ''The neuronal microtubule-associated protein tau is a substrate for caspase-3 and an effector of apoptosis.''; PubMed Europe PMC Scholia
  6. Cirillo N, Lanza M, De Rosa A, Cammarota M, La Gatta A, Gombos F, Lanza A.; ''The most widespread desmosomal cadherin, desmoglein 2, is a novel target of caspase 3-mediated apoptotic machinery.''; PubMed Europe PMC Scholia
  7. Qian J, Steigerwald K, Combs KA, Barton MC, Groden J.; ''Caspase cleavage of the APC tumor suppressor and release of an amino-terminal domain is required for the transcription-independent function of APC in apoptosis.''; PubMed Europe PMC Scholia
  8. Steinhusen U, Weiske J, Badock V, Tauber R, Bommert K, Huber O.; ''Cleavage and shedding of E-cadherin after induction of apoptosis.''; PubMed Europe PMC Scholia
  9. Jänicke RU, Ng P, Sprengart ML, Porter AG.; ''Caspase-3 is required for alpha-fodrin cleavage but dispensable for cleavage of other death substrates in apoptosis.''; PubMed Europe PMC Scholia
  10. Jung JH, Traugh JA.; ''Regulation of the interaction of Pak2 with Cdc42 via autophosphorylation of serine 141.''; PubMed Europe PMC Scholia
  11. Datta R, Kojima H, Yoshida K, Kufe D.; ''Caspase-3-mediated cleavage of protein kinase C theta in induction of apoptosis.''; PubMed Europe PMC Scholia
  12. Kamada S, Kikkawa U, Tsujimoto Y, Hunter T.; ''Nuclear translocation of caspase-3 is dependent on its proteolytic activation and recognition of a substrate-like protein(s).''; PubMed Europe PMC Scholia
  13. Byun Y, Chen F, Chang R, Trivedi M, Green KJ, Cryns VL.; ''Caspase cleavage of vimentin disrupts intermediate filaments and promotes apoptosis.''; PubMed Europe PMC Scholia
  14. Morishima N.; ''Changes in nuclear morphology during apoptosis correlate with vimentin cleavage by different caspases located either upstream or downstream of Bcl-2 action.''; PubMed Europe PMC Scholia
  15. Neimanis S, Albig W, Doenecke D, Kahle J.; ''Sequence elements in both subunits of the DNA fragmentation factor are essential for its nuclear transport.''; PubMed Europe PMC Scholia
  16. Mizuno K, Noda K, Araki T, Imaoka T, Kobayashi Y, Akita Y, Shimonaka M, Kishi S, Ohno S.; ''The proteolytic cleavage of protein kinase C isotypes, which generates kinase and regulatory fragments, correlates with Fas-mediated and 12-O-tetradecanoyl-phorbol-13-acetate-induced apoptosis.''; PubMed Europe PMC Scholia
  17. Blanchard H, Kodandapani L, Mittl PR, Marco SD, Krebs JF, Wu JC, Tomaselli KJ, Grütter MG.; ''The three-dimensional structure of caspase-8: an initiator enzyme in apoptosis.''; PubMed Europe PMC Scholia
  18. Orth K, Chinnaiyan AM, Garg M, Froelich CJ, Dixit VM.; ''The CED-3/ICE-like protease Mch2 is activated during apoptosis and cleaves the death substrate lamin A.''; PubMed Europe PMC Scholia
  19. Widlak P, Kalinowska M, Parseghian MH, Lu X, Hansen JC, Garrard WT.; ''The histone H1 C-terminal domain binds to the apoptotic nuclease, DNA fragmentation factor (DFF40/CAD) and stimulates DNA cleavage.''; PubMed Europe PMC Scholia
  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
  21. Widlak P, Li P, Wang X, Garrard WT.; ''Cleavage preferences of the apoptotic endonuclease DFF40 (caspase-activated DNase or nuclease) on naked DNA and chromatin substrates.''; PubMed Europe PMC Scholia
  22. Brancolini C, Benedetti M, Schneider C.; ''Microfilament reorganization during apoptosis: the role of Gas2, a possible substrate for ICE-like proteases.''; PubMed Europe PMC Scholia
  23. Chang J, Xie M, Shah VR, Schneider MD, Entman ML, Wei L, Schwartz RJ.; ''Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis.''; PubMed Europe PMC Scholia
  24. Lazebnik YA, Takahashi A, Poirier GG, Kaufmann SH, Earnshaw WC.; ''Characterization of the execution phase of apoptosis in vitro using extracts from condemned-phase cells.''; PubMed Europe PMC Scholia
  25. Riedl SJ, Fuentes-Prior P, Renatus M, Kairies N, Krapp S, Huber R, Salvesen GS, Bode W.; ''Structural basis for the activation of human procaspase-7.''; PubMed Europe PMC Scholia
  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
  28. Weiske J, Schöneberg T, Schröder W, Hatzfeld M, Tauber R, Huber O.; ''The fate of desmosomal proteins in apoptotic cells.''; PubMed Europe PMC Scholia
  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
  31. Chandra D, Choy G, Deng X, Bhatia B, Daniel P, Tang DG.; ''Association of active caspase 8 with the mitochondrial membrane during apoptosis: potential roles in cleaving BAP31 and caspase 3 and mediating mitochondrion-endoplasmic reticulum cross talk in etoposide-induced cell death.''; PubMed Europe PMC Scholia
  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
  39. Fischer U, Jänicke RU, Schulze-Osthoff K.; ''Many cuts to ruin: a comprehensive update of caspase substrates.''; PubMed Europe PMC Scholia
  40. Sahara S, Aoto M, Eguchi Y, Imamoto N, Yoneda Y, Tsujimoto Y.; ''Acinus is a caspase-3-activated protein required for apoptotic chromatin condensation.''; PubMed Europe PMC Scholia
  41. Hanus J, Kalinowska-Herok M, Widlak P.; ''The major apoptotic endonuclease DFF40/CAD is a deoxyribose-specific and double-strand-specific enzyme.''; PubMed Europe PMC Scholia
  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
  47. Wen LP, Fahrni JA, Troie S, Guan JL, Orth K, Rosen GD.; ''Cleavage of focal adhesion kinase by caspases during apoptosis.''; PubMed Europe PMC Scholia
  48. Rao L, Perez D, White E.; ''Lamin proteolysis facilitates nuclear events during apoptosis.''; PubMed Europe PMC Scholia
  49. Dan I, Ong SE, Watanabe NM, Blagoev B, Nielsen MM, Kajikawa E, Kristiansen TZ, Mann M, Pandey A.; ''Cloning of MASK, a novel member of the mammalian germinal center kinase III subfamily, with apoptosis-inducing properties.''; PubMed Europe PMC Scholia
  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


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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


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:456216 (ChEBI)
APC(1-777)ProteinP25054 (Uniprot-TrEMBL)
APC(778-2843)ProteinP25054 (Uniprot-TrEMBL)
APCProteinP25054 (Uniprot-TrEMBL)
ATPMetaboliteCHEBI:30616 (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) ProteinP42574 (Uniprot-TrEMBL)
CASP3(29-175) ProteinP42574 (Uniprot-TrEMBL)
CASP6(194-293) ProteinP55212 (Uniprot-TrEMBL)
CASP6(24-179) ProteinP55212 (Uniprot-TrEMBL)
CASP7(207-303) ProteinP55210 (Uniprot-TrEMBL)
CASP7(24-198) ProteinP55210 (Uniprot-TrEMBL)
CASP8(217-374) ProteinQ14790 (Uniprot-TrEMBL)
CASP8(385-479) 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 ProteinP35222 (Uniprot-TrEMBL)
CTNNB1(1-115)ProteinP35222 (Uniprot-TrEMBL)
CTNNB1(116-376)ProteinP35222 (Uniprot-TrEMBL)
Caspase cleaved DFFA (117)ComplexR-HSA-211208 (Reactome)
Caspase-3, Caspase-7ComplexR-HSA-202877 (Reactome)
Caspase-3ComplexR-HSA-350870 (Reactome)
Caspase-7ComplexR-HSA-141643 (Reactome) CASP7 heterotetramer consists of two anti-parallel arranged CASP7 heterodimers, each one formed by a 20 kDa (p20) and a 11 kDa (p11) subunit.
DBNL(1-361)ProteinQ9UJU6 (Uniprot-TrEMBL)
DBNL(362-431)ProteinQ9UJU6 (Uniprot-TrEMBL)
DBNLProteinQ9UJU6 (Uniprot-TrEMBL)
DFF cleaved DNA fragments R-ALL-211242 (Reactome)
DFF cleaved DNAComplexR-HSA-211254 (Reactome)
DFF40 homodimer/homooligomerComplexR-HSA-353623 (Reactome)
DFF40 associated with chromatinComplexR-HSA-211253 (Reactome)
DFF40 homodimerComplexR-HSA-350273 (Reactome)
DFF40 homooligomer R-HSA-350274 (Reactome)

with the

importin-alpha:importin-beta complex
ComplexR-HSA-350287 (Reactome)

with the

importin-alpha:importin-beta complex
ComplexR-HSA-350304 (Reactome)
DFFA ProteinO00273 (Uniprot-TrEMBL)
DFFA(1-117) ProteinO00273 (Uniprot-TrEMBL)
DFFA(1-117)ProteinO00273 (Uniprot-TrEMBL)
DFFA(1-?) ProteinO00273 (Uniprot-TrEMBL)
DFFA(118-224) ProteinO00273 (Uniprot-TrEMBL)
DFFA(118-224)ProteinO00273 (Uniprot-TrEMBL)
DFFA(118-331) ProteinO00273 (Uniprot-TrEMBL)
DFFA(225-331) ProteinO00273 (Uniprot-TrEMBL)
DFFA(225-331)ProteinO00273 (Uniprot-TrEMBL)
DFFA:DFFBComplexR-HSA-211192 (Reactome)
DFFA:DFFBComplexR-HSA-211225 (Reactome)
DFFAProteinO00273 (Uniprot-TrEMBL)
DFFB ProteinO76075 (Uniprot-TrEMBL)
DFFBProteinO76075 (Uniprot-TrEMBL)
DNA R-ALL-29428 (Reactome)
DNAR-ALL-29428 (Reactome)
DNM1LProteinO00429 (Uniprot-TrEMBL)
DSG1(50-888)ProteinQ02413 (Uniprot-TrEMBL)
DSG1(889-1049)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(28-403)ProteinP06396 (Uniprot-TrEMBL)
GSN(404-782)ProteinP06396 (Uniprot-TrEMBL)
GSNProteinP06396 (Uniprot-TrEMBL)
H1F0 ProteinP07305 (Uniprot-TrEMBL)
HIST1H1A ProteinQ02539 (Uniprot-TrEMBL)
HIST1H1B ProteinP16401 (Uniprot-TrEMBL)
HIST1H1C ProteinP16403 (Uniprot-TrEMBL)
HIST1H1D ProteinP16402 (Uniprot-TrEMBL)
HIST1H1E ProteinP10412 (Uniprot-TrEMBL)
HMGB1 ProteinP09429 (Uniprot-TrEMBL)
HMGB1/HMGB2- bound chromatinComplexR-HSA-266207 (Reactome)
HMGB1/HMGB2ComplexR-HSA-266214 (Reactome)
HMGB2 ProteinP26583 (Uniprot-TrEMBL)
Histone H1 bound chromatin DNAComplexR-HSA-211238 (Reactome)
KPNA1 ProteinP52294 (Uniprot-TrEMBL)
KPNB1 ProteinQ14974 (Uniprot-TrEMBL)
LMNA(1-230)ProteinP02545-1 (Uniprot-TrEMBL)
LMNA(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(213-524)ProteinQ13177 (Uniprot-TrEMBL)
PAK2ProteinQ13177 (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(330-676)ProteinQ05655 (Uniprot-TrEMBL)
PRKCDProteinQ05655 (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(1114-1354)ProteinQ13464 (Uniprot-TrEMBL)
ROCK1ProteinQ13464 (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(314-443)ProteinQ9Y6E0 (Uniprot-TrEMBL)
STK24ProteinQ9Y6E0 (Uniprot-TrEMBL)
TJP1 (?-?)ProteinQ07157 (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-3ComplexR-HSA-211223 (Reactome) CASP3 heterotetramer consists of two anti-parallel arranged CASP3 heterodimers, each one formed by a 17 kDa (p17) and a 12 kDa (p12) subunit.
active caspase-6ComplexR-HSA-350324 (Reactome) CASP6 heterotetramer consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 11 kDa (p11) subunit.
active caspase-6ComplexR-HSA-352255 (Reactome) CASP6 heterotetramer consists of two anti-parallel arranged heterodimers, each one formed by a 18 kDa (p18) and a 11 kDa (p11) subunit.
active caspase-7ComplexR-HSA-351937 (Reactome) CASP7 heterotetramer consists of two anti-parallel arranged CASP7 heterodimers, each one formed by a 20 kDa (p20) and a 11 kDa (p11) subunit.
active caspase-8ComplexR-HSA-2562550 (Reactome)
active caspase-8ComplexR-HSA-2671818 (Reactome)
beta-cateninComplexR-HSA-191727 (Reactome)

DFFA (117,224):DFFB

ComplexR-HSA-211196 (Reactome)
importin-alpha:importin-beta complexComplexR-HSA-350267 (Reactome)
importin-alpha:importin-betaComplexR-HSA-350277 (Reactome)
p-5S-PAK2(2-212)ProteinQ13177 (Uniprot-TrEMBL)
p-5S-PAK2ProteinQ13177 (Uniprot-TrEMBL)
p-T402-PAK2(213-524)ProteinQ13177 (Uniprot-TrEMBL)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
ACIN1(1-1093)ArrowR-HSA-201630 (Reactome)
ACIN1(1094-1341)ArrowR-HSA-201630 (Reactome)
ACIN1R-HSA-201630 (Reactome)
ADD1(1-633)ArrowR-HSA-201608 (Reactome)
ADD1(634-737)ArrowR-HSA-201608 (Reactome)
ADD1R-HSA-201608 (Reactome)
ADPArrowR-HSA-211583 (Reactome)
ADPArrowR-HSA-211650 (Reactome)
APC(1-777)ArrowR-HSA-202947 (Reactome)
APC(778-2843)ArrowR-HSA-202947 (Reactome)
APCR-HSA-202947 (Reactome)
ATPR-HSA-211583 (Reactome)
ATPR-HSA-211650 (Reactome)
BCAP31(165-237)ArrowR-HSA-351894 (Reactome)
BCAP31(2-164)ArrowR-HSA-351894 (Reactome)
BCAP31(2-164)ArrowR-HSA-351948 (Reactome)
BCAP31(2-245)R-HSA-351894 (Reactome)
BCAP31(238-246)ArrowR-HSA-351894 (Reactome)
BIRC2(1-372)ArrowR-HSA-202960 (Reactome)
BIRC2(373-618)ArrowR-HSA-202960 (Reactome)
BIRC2R-HSA-202960 (Reactome)
BMX(1-242)ArrowR-HSA-351849 (Reactome)
BMX(243-675)ArrowR-HSA-351849 (Reactome)
BMXR-HSA-351849 (Reactome)
CDH1(155-750)ArrowR-HSA-202939 (Reactome)
CDH1(155-882)R-HSA-202939 (Reactome)
CDH1(751-882)ArrowR-HSA-202939 (Reactome)
CLSPN(1-1072)ArrowR-HSA-351936 (Reactome)
CLSPN(1073-1332)ArrowR-HSA-351936 (Reactome)
CLSPNR-HSA-351936 (Reactome)
CTNNB1(1-115)ArrowR-HSA-202969 (Reactome)
CTNNB1(116-376)ArrowR-HSA-202969 (Reactome)
Caspase cleaved DFFA (117)ArrowR-HSA-211190 (Reactome)
Caspase cleaved DFFA (117)R-HSA-211186 (Reactome)
Caspase-3, Caspase-7mim-catalysisR-HSA-201628 (Reactome)
Caspase-3, Caspase-7mim-catalysisR-HSA-201639 (Reactome)
Caspase-3, Caspase-7mim-catalysisR-HSA-351901 (Reactome)
Caspase-3R-HSA-211219 (Reactome)
Caspase-3mim-catalysisR-HSA-201595 (Reactome)
Caspase-3mim-catalysisR-HSA-201603 (Reactome)
Caspase-3mim-catalysisR-HSA-201608 (Reactome)
Caspase-3mim-catalysisR-HSA-201611 (Reactome)
Caspase-3mim-catalysisR-HSA-201622 (Reactome)
Caspase-3mim-catalysisR-HSA-201629 (Reactome)
Caspase-3mim-catalysisR-HSA-201630 (Reactome)
Caspase-3mim-catalysisR-HSA-201631 (Reactome)
Caspase-3mim-catalysisR-HSA-201636 (Reactome)
Caspase-3mim-catalysisR-HSA-201640 (Reactome)
Caspase-3mim-catalysisR-HSA-202917 (Reactome)
Caspase-3mim-catalysisR-HSA-202939 (Reactome)
Caspase-3mim-catalysisR-HSA-202947 (Reactome)
Caspase-3mim-catalysisR-HSA-202960 (Reactome)
Caspase-3mim-catalysisR-HSA-202966 (Reactome)
Caspase-3mim-catalysisR-HSA-202967 (Reactome)
Caspase-3mim-catalysisR-HSA-202969 (Reactome)
Caspase-3mim-catalysisR-HSA-211651 (Reactome)
Caspase-3mim-catalysisR-HSA-212552 (Reactome)
Caspase-3mim-catalysisR-HSA-350651 (Reactome)
Caspase-3mim-catalysisR-HSA-351849 (Reactome)
Caspase-3mim-catalysisR-HSA-351871 (Reactome)
Caspase-3mim-catalysisR-HSA-351876 (Reactome)
Caspase-3mim-catalysisR-HSA-351877 (Reactome)
Caspase-3mim-catalysisR-HSA-351913 (Reactome)
Caspase-7R-HSA-9029680 (Reactome)
Caspase-7mim-catalysisR-HSA-201634 (Reactome)
DBNL(1-361)ArrowR-HSA-202966 (Reactome)
DBNL(362-431)ArrowR-HSA-202966 (Reactome)
DBNLR-HSA-202966 (Reactome)
DFF cleaved DNAArrowR-HSA-211247 (Reactome)
DFF40 homodimer/homooligomerArrowR-HSA-211247 (Reactome)
DFF40 homodimer/homooligomerR-HSA-211239 (Reactome)
DFF40 associated with chromatinArrowR-HSA-211239 (Reactome)
DFF40 associated with chromatinR-HSA-211247 (Reactome)
DFF40 associated with chromatinmim-catalysisR-HSA-211247 (Reactome)
DFF40 homodimerArrowR-HSA-211193 (Reactome)

with the

importin-alpha:importin-beta complex
ArrowR-HSA-211191 (Reactome)

with the

importin-alpha:importin-beta complex
ArrowR-HSA-211206 (Reactome)

with the

importin-alpha:importin-beta complex
R-HSA-211206 (Reactome)

with the

importin-alpha:importin-beta complex
R-HSA-9029667 (Reactome)
DFFA(1-117)ArrowR-HSA-211207 (Reactome)
DFFA(118-224)ArrowR-HSA-211207 (Reactome)
DFFA(225-331)ArrowR-HSA-211207 (Reactome)
DFFA:DFFBArrowR-HSA-211224 (Reactome)
DFFA:DFFBArrowR-HSA-9029667 (Reactome)
DFFA:DFFBR-HSA-211190 (Reactome)
DFFA:DFFBR-HSA-211191 (Reactome)
DFFAR-HSA-211224 (Reactome)
DFFBArrowR-HSA-211207 (Reactome)
DFFBR-HSA-211193 (Reactome)
DFFBR-HSA-211224 (Reactome)
DNAR-HSA-266204 (Reactome)
DNM1LArrowR-HSA-351948 (Reactome)
DNM1LR-HSA-351948 (Reactome)
DSG1(50-888)ArrowR-HSA-202917 (Reactome)
DSG1(889-1049)ArrowR-HSA-202917 (Reactome)
DSG1R-HSA-202917 (Reactome)
DSG2(?-1118)ArrowR-HSA-351877 (Reactome)
DSG2R-HSA-351877 (Reactome)
DSG3(50-781)ArrowR-HSA-201631 (Reactome)
DSG3(782-999)ArrowR-HSA-201631 (Reactome)
DSG3R-HSA-201631 (Reactome)
DSP(?-?)ArrowR-HSA-201636 (Reactome)
DSPR-HSA-201636 (Reactome)
FNTA(1-59)ArrowR-HSA-201640 (Reactome)
FNTA(2-379)R-HSA-201640 (Reactome)
FNTA(59-379)ArrowR-HSA-201640 (Reactome)
GAS2(1-279)ArrowR-HSA-201639 (Reactome)
GAS2(280-313)ArrowR-HSA-201639 (Reactome)
GAS2R-HSA-201639 (Reactome)
GSN(28-403)ArrowR-HSA-201622 (Reactome)
GSN(404-782)ArrowR-HSA-201622 (Reactome)
GSNR-HSA-201622 (Reactome)
HMGB1/HMGB2- bound chromatinArrowR-HSA-211247 (Reactome)
HMGB1/HMGB2- bound chromatinArrowR-HSA-266204 (Reactome)
HMGB1/HMGB2R-HSA-266204 (Reactome)
Histone H1 bound chromatin DNAR-HSA-211239 (Reactome)
LMNA(1-230)ArrowR-HSA-264865 (Reactome)
LMNA(231-664)ArrowR-HSA-264865 (Reactome)
LMNB1(1-231)ArrowR-HSA-264871 (Reactome)
LMNB1(232-586)ArrowR-HSA-264871 (Reactome)
LMNB1R-HSA-264871 (Reactome)
Lamin AR-HSA-264865 (Reactome)
MAPT(2-421)ArrowR-HSA-201629 (Reactome)
MAPT(422-758)ArrowR-HSA-201629 (Reactome)
MAPTR-HSA-201629 (Reactome)
MST4(1-305)ArrowR-HSA-350651 (Reactome)
MST4(306-416)ArrowR-HSA-350651 (Reactome)
MST4R-HSA-350651 (Reactome)
OCLN(1-320)ArrowR-HSA-351876 (Reactome)
OCLN(321-522)ArrowR-HSA-351876 (Reactome)
OCLNR-HSA-351876 (Reactome)
PAK2(213-524)ArrowR-HSA-211651 (Reactome)
PAK2(213-524)R-HSA-211650 (Reactome)
PAK2(213-524)mim-catalysisR-HSA-211650 (Reactome)
PAK2R-HSA-211583 (Reactome)
PAK2mim-catalysisR-HSA-211583 (Reactome)
PKP1(?-?)ArrowR-HSA-201595 (Reactome)
PKP1R-HSA-201595 (Reactome)
PLEC(1-2395)ArrowR-HSA-201637 (Reactome)
PLEC(2396-4684)ArrowR-HSA-201637 (Reactome)
PLECR-HSA-201637 (Reactome)
PRKCD(1-329)ArrowR-HSA-212552 (Reactome)
PRKCD(330-676)ArrowR-HSA-212552 (Reactome)
PRKCDR-HSA-212552 (Reactome)
PRKCQ(1-354)ArrowR-HSA-201603 (Reactome)
PRKCQ(355-706)ArrowR-HSA-201603 (Reactome)
PRKCQR-HSA-201603 (Reactome)
PTK2(1-772)ArrowR-HSA-201634 (Reactome)
PTK2(773-1052)ArrowR-HSA-201634 (Reactome)
PTK2R-HSA-201634 (Reactome)
R-HSA-201595 (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 impaired in supporting the formation and maintenance of desmosomes during apoptosis (Weiske et al., 2001). Caspase-3 inhibition prevents cleavage of Plakophilin-1, implicating Caspase-3 as the responsible endopeptidase (Weiske et al. 2001).
R-HSA-201603 (Reactome) Cleavage of PKCtheta by Caspase-3 induces nuclear fragmentation and lethality (Datta et al., 1997)
R-HSA-201608 (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).
R-HSA-201611 (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).
R-HSA-201622 (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)
R-HSA-201628 (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).
R-HSA-201629 (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).
R-HSA-201630 (Reactome) Acinus induces apoptotic chromatin condensation after cleavage and activation by CASP3 (Sahara et al., 1999).
R-HSA-201631 (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).
R-HSA-201634 (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).
R-HSA-201636 (Reactome) Cleavage of desmosomal proteins including desmoplakin contributes to cell rounding and disintegration of the intermediate filament system (Weiske et al., 2001). Caspase-3 inhibition prevents desmoplakin cleavage, implicating caspase-3 as the responsible endopeptidase (Weiske et al. 2001).
R-HSA-201637 (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).
R-HSA-201639 (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).
R-HSA-201640 (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).
R-HSA-202917 (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).
R-HSA-202939 (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).
R-HSA-202947 (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).
R-HSA-202960 (Reactome) c-IAP1 is cleaved by caspase-3 producing a proapoptotic C-terminal fragment.
R-HSA-202966 (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).
R-HSA-202967 (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).
R-HSA-202969 (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 ).
R-HSA-211186 (Reactome) Caspase-3 cleaves DFF45 between residues 224,225.
R-HSA-211190 (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).
R-HSA-211191 (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).
R-HSA-211193 (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).
R-HSA-211206 (Reactome) DFF associated with alpha-importin:beta-importin is translocated to the nucleus (Neimanis et al., 2007)
R-HSA-211207 (Reactome) Following caspase-3 cleavage, the fragments of DFF45 dissociate from DFF40, the active component of DFF (Liu et al. 1998).
R-HSA-211219 (Reactome) Active caspase-3 is translocated from the cytoplasm to the nucleus during progression through apoptosis (Kamada et al., 2005).
R-HSA-211224 (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).
R-HSA-211239 (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).
R-HSA-211247 (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).
R-HSA-211583 (Reactome) Inactive PAK-2 can be partially autophosphorylated in the regulatory region without being activated (Gatti et al. 1999).
R-HSA-211650 (Reactome) Activation of PAK-2p34 coincides with autophosphorylation of Thr 402 in the the catalytic domain (Walter et al., 1998).
R-HSA-211651 (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.
R-HSA-211712 (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).
R-HSA-212552 (Reactome) Caspase mediated cleavage produces a constitutively active kinase that induces apoptosis (Ghayur et al.,1996).
R-HSA-264865 (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).
R-HSA-264871 (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).
R-HSA-266204 (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).
R-HSA-350318 (Reactome)