Regulation of Apoptosis (Homo sapiens)

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4, 5311cytosolUBC(533-608) PSMD6 UBC(305-380) PSMB10 UBB(153-228) PSMC6 PSMD10 PSMD13 PSMB1 PSMC2 PSMD8 UBC(457-532) PSMD12 PSMD4 PSMB3 PSMD2 p-T402-PAK2(213-524) PSMA5 PAK-2p34:RHG10complexPSMD14 PSMD5 26S proteasomePSMB5 PSMD3 PSMA6 PSMF1 K48polyUb-p-T402-PAK-2p43RPS27A(1-76) PSMC4 UBA52(1-76) PSME3 PSMD1 PSMD11 PSMB9 PSMA2 PSMC3 ARHGAP10PSMB2 PSMC1 UBB(77-152) PSME2 PSMB11 PSMA4 ARHGAP10 UBC(77-152) PSMA3 perinuclearPAK-2p34:RHG10complexPSMC5 PSMA7 ARHGAP10 PSMB4 UbPSMA8 PSMB7 UBC(229-304) p-T402-PAK2(213-524) PSME1 PSMA1 Ubiquitin ligaseUBC(609-684) PSMD9 UBC(153-228) UBC(1-76) p-T402-PAK2(213-524)UBC(381-456) UBB(1-76) PSMB6 PSME4 PSMD7 PSMB8 2


Description

A regulated balance between cell survival and apoptosis is essential for normal

development and homeostasis of multicellular organisms (see Matsuzawa, 2001). Defects in control of this balance may contribute to autoimmune disease, neurodegeneration and cancer. Protein ubiquitination and degradation is one of the major mechanisms that regulate apoptotic cell death (reviewed in Yang and Yu 2003).

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Bibliography

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  1. Matsuzawa A, Ichijo H.; ''Molecular mechanisms of the decision between life and death: regulation of apoptosis by apoptosis signal-regulating kinase 1.''; PubMed Europe PMC Scholia
  2. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  3. Wei SJ, Williams JG, Dang H, Darden TA, Betz BL, Humble MM, Chang FM, Trempus CS, Johnson K, Cannon RE, Tennant RW.; ''Identification of a specific motif of the DSS1 protein required for proteasome interaction and p53 protein degradation.''; PubMed Europe PMC Scholia
  4. Yang Y, Yu X.; ''Regulation of apoptosis: the ubiquitous way.''; PubMed Europe PMC Scholia
  5. Koeppel MA, McCarthy CC, Moertl E, Jakobi R.; ''Identification and characterization of PS-GAP as a novel regulator of caspase-activated PAK-2.''; PubMed Europe PMC Scholia
  6. Head B, Griparic L, Amiri M, Gandre-Babbe S, van der Bliek AM.; ''Inducible proteolytic inactivation of OPA1 mediated by the OMA1 protease in mammalian cells.''; PubMed Europe PMC Scholia
  7. Jakobi R, McCarthy CC, Koeppel MA, Stringer DK.; ''Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradation.''; PubMed Europe PMC Scholia
  8. Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF.; ''Inherited mitochondrial optic neuropathies.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
101467view11:33, 1 November 2018ReactomeTeamreactome version 66
101005view21:12, 31 October 2018ReactomeTeamreactome version 65
100541view19:46, 31 October 2018ReactomeTeamreactome version 64
100089view16:31, 31 October 2018ReactomeTeamreactome version 63
99639view15:02, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99242view12:44, 31 October 2018ReactomeTeamreactome version 62
93753view13:34, 16 August 2017ReactomeTeamreactome version 61
93273view11:19, 9 August 2017ReactomeTeamreactome version 61
86350view09:15, 11 July 2016ReactomeTeamreactome version 56
83218view10:25, 18 November 2015ReactomeTeamVersion54
81608view13:09, 21 August 2015ReactomeTeamVersion53
77071view08:37, 17 July 2014ReactomeTeamFixed remaining interactions
76776view12:14, 16 July 2014ReactomeTeamFixed remaining interactions
76099view10:16, 11 June 2014ReactomeTeamRe-fixing comment source
75811view11:35, 10 June 2014ReactomeTeamReactome 48 Update
75161view14:10, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74808view08:54, 30 April 2014ReactomeTeamReactome46
69017view17:47, 8 July 2013MaintBotUpdated to 2013 gpml schema
45054view19:23, 6 October 2011ThomasOntology Term : 'apoptotic cell death pathway' added !
42112view21:57, 4 March 2011MaintBotAutomatic update
39922view05:56, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
26S proteasomeComplexR-HSA-68819 (Reactome)
ARHGAP10 ProteinA1A4S6 (Uniprot-TrEMBL)
ARHGAP10ProteinA1A4S6 (Uniprot-TrEMBL)
K48polyUb-p-T402-PAK-2p43ProteinQ13177 (Uniprot-TrEMBL)
PAK-2p34:RHG10 complexComplexR-HSA-211701 (Reactome)
PSMA1 ProteinP25786 (Uniprot-TrEMBL)
PSMA2 ProteinP25787 (Uniprot-TrEMBL)
PSMA3 ProteinP25788 (Uniprot-TrEMBL)
PSMA4 ProteinP25789 (Uniprot-TrEMBL)
PSMA5 ProteinP28066 (Uniprot-TrEMBL)
PSMA6 ProteinP60900 (Uniprot-TrEMBL)
PSMA7 ProteinO14818 (Uniprot-TrEMBL)
PSMA8 ProteinQ8TAA3 (Uniprot-TrEMBL)
PSMB1 ProteinP20618 (Uniprot-TrEMBL)
PSMB10 ProteinP40306 (Uniprot-TrEMBL)
PSMB11 ProteinA5LHX3 (Uniprot-TrEMBL)
PSMB2 ProteinP49721 (Uniprot-TrEMBL)
PSMB3 ProteinP49720 (Uniprot-TrEMBL)
PSMB4 ProteinP28070 (Uniprot-TrEMBL)
PSMB5 ProteinP28074 (Uniprot-TrEMBL)
PSMB6 ProteinP28072 (Uniprot-TrEMBL)
PSMB7 ProteinQ99436 (Uniprot-TrEMBL)
PSMB8 ProteinP28062 (Uniprot-TrEMBL)
PSMB9 ProteinP28065 (Uniprot-TrEMBL)
PSMC1 ProteinP62191 (Uniprot-TrEMBL)
PSMC2 ProteinP35998 (Uniprot-TrEMBL)
PSMC3 ProteinP17980 (Uniprot-TrEMBL)
PSMC4 ProteinP43686 (Uniprot-TrEMBL)
PSMC5 ProteinP62195 (Uniprot-TrEMBL)
PSMC6 ProteinP62333 (Uniprot-TrEMBL)
PSMD1 ProteinQ99460 (Uniprot-TrEMBL)
PSMD10 ProteinO75832 (Uniprot-TrEMBL)
PSMD11 ProteinO00231 (Uniprot-TrEMBL)
PSMD12 ProteinO00232 (Uniprot-TrEMBL)
PSMD13 ProteinQ9UNM6 (Uniprot-TrEMBL)
PSMD14 ProteinO00487 (Uniprot-TrEMBL)
PSMD2 ProteinQ13200 (Uniprot-TrEMBL)
PSMD3 ProteinO43242 (Uniprot-TrEMBL)
PSMD4 ProteinP55036 (Uniprot-TrEMBL)
PSMD5 ProteinQ16401 (Uniprot-TrEMBL)
PSMD6 ProteinQ15008 (Uniprot-TrEMBL)
PSMD7 ProteinP51665 (Uniprot-TrEMBL)
PSMD8 ProteinP48556 (Uniprot-TrEMBL)
PSMD9 ProteinO00233 (Uniprot-TrEMBL)
PSME1 ProteinQ06323 (Uniprot-TrEMBL)
PSME2 ProteinQ9UL46 (Uniprot-TrEMBL)
PSME3 ProteinP61289 (Uniprot-TrEMBL)
PSME4 ProteinQ14997 (Uniprot-TrEMBL)
PSMF1 ProteinQ92530 (Uniprot-TrEMBL)
RPS27A(1-76) ProteinP62979 (Uniprot-TrEMBL)
UBA52(1-76) ProteinP62987 (Uniprot-TrEMBL)
UBB(1-76) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(153-228) ProteinP0CG47 (Uniprot-TrEMBL)
UBB(77-152) ProteinP0CG47 (Uniprot-TrEMBL)
UBC(1-76) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(153-228) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(229-304) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(305-380) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(381-456) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(457-532) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(533-608) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(609-684) ProteinP0CG48 (Uniprot-TrEMBL)
UBC(77-152) ProteinP0CG48 (Uniprot-TrEMBL)
UbComplexR-HSA-113595 (Reactome)
Ubiquitin ligaseR-HSA-69593 (Reactome)
p-T402-PAK2(213-524) ProteinQ13177 (Uniprot-TrEMBL)
p-T402-PAK2(213-524)ProteinQ13177 (Uniprot-TrEMBL)
perinuclear

PAK-2p34:RHG10

complex
ComplexR-HSA-211729 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
26S proteasomemim-catalysisR-HSA-211715 (Reactome)
ARHGAP10R-HSA-211716 (Reactome)
K48polyUb-p-T402-PAK-2p43ArrowR-HSA-211734 (Reactome)
K48polyUb-p-T402-PAK-2p43R-HSA-211715 (Reactome)
PAK-2p34:RHG10 complexArrowR-HSA-211716 (Reactome)
PAK-2p34:RHG10 complexR-HSA-211731 (Reactome)
R-HSA-211715 (Reactome) Proteolytically activated PAK-2p34, but not full-length PAK-2, is degraded rapidly by the proteasome (Jakobi et al., 2003). Here, degradation of PAK-2p34 is described as occurring in the cytosol. However, to date it is not known whether this occurs in the nucleus or in the cytoplasm.
R-HSA-211716 (Reactome) Murine PS-GAP interacts specifically with caspase-activated PAK-2p34, but not active or inactive full-length PAK-2, through a region between the GAP and SH3 domains (Koeppel et al.,2004). Evidence for this reaction comes from experiments using both mouse and rabbit proteins.
R-HSA-211731 (Reactome) Following caspase mediated cleavage, PAK-2p34 translocates to the nucleus (Jakobi et al., 2003). The interaction with PS-GAP changes the localization of PAK-2p34 from the nucleus to the perinuclear region (Koeppel et al.,2004).
R-HSA-211734 (Reactome) PAK-2p34 is ubiquitinated prior to degradation (Jakobi et al., 2003). Here, ubiquitination of PAK-2p34 is described as occurring in the cytosol. However, to date it is not known whether this occurs in the nucleus or in the cytoplasm. Evidence for this reaction comes from experiments using both human and rabbit proteins. The polyubiquitin synthesized in the reaction is inferred to contain lysine-48 (K48) linkages because the modified protein is targeted to the proteasome (Komander 2009).
UbArrowR-HSA-211715 (Reactome)
UbR-HSA-211734 (Reactome)
Ubiquitin ligasemim-catalysisR-HSA-211734 (Reactome)
p-T402-PAK2(213-524)R-HSA-211716 (Reactome)
p-T402-PAK2(213-524)R-HSA-211734 (Reactome)
perinuclear

PAK-2p34:RHG10

complex
ArrowR-HSA-211731 (Reactome)
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