Regulation of apoptosis (Homo sapiens)

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224, 64, 613, 6, 74, 9endosome membranecytosolDCC:DIP13alpha:Caspase-9Unc5B with death domain:DAPKPAK-2p34:RHG10 complexGraf-2/ Arhgap10UNC5B fragment with death domainUNC5Aunidentified caspase26S proteasomeNRAGEphospho-PAK-2p34 (Thr 402)UNC5A:NRAGEProtease/caspase cleaved UNC5B fragment bound to PMactive caspase-3UNC5A fragment with death domainubiquitinated PAK-2p34DCCDCC's inhibitory C-terminal domainUbiquitin ligaseProtease/caspase cleaved UNC5A fragment bound to PMperinuclear PAK-2p34:RHG10 complexpolyubiquitinated PAK-2p34ubiquitinCaspase-3 precursorUNC5BDCC:DIP13alphaDCC-interacting protein 13-alphaDAPKsATPADPCleaved Caspase-9DCC's fragment with the ADD domain85105


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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Ontology Terms

 

Bibliography

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  1. Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF.; ''Inherited mitochondrial optic neuropathies.''; PubMed Europe PMC Scholia
  2. 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
  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. Jakobi R, McCarthy CC, Koeppel MA, Stringer DK.; ''Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradation.''; 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. Yang Y, Yu X.; ''Regulation of apoptosis: the ubiquitous way.''; PubMed Europe PMC Scholia
  7. Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
  8. 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

History

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CompareRevisionActionTimeUserComment
118168view10:45, 25 May 2021EweitzModified title
114898view16:41, 25 January 2021ReactomeTeamReactome version 75
113344view11:41, 2 November 2020ReactomeTeamReactome version 74
112553view15:52, 9 October 2020ReactomeTeamReactome version 73
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

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NameTypeDatabase referenceComment
26S

proteasome

ComplexREACT_2353 (Reactome)
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)
Caspase-3

precursor

ProteinP42574 (UniProt)
Cleaved Caspase-9 ComplexREACT_5782 (Reactome)
DAPKs ProteinREACT_22954 (Reactome)
DCC ProteinP43146 (UniProt)
DCC's fragment with

the ADD domain

ProteinP43146 (UniProt)
DCC's inhibitory C-

terminal domain

ProteinP43146 (UniProt)
DCC-interacting

protein 13-alpha

ProteinQ9UKG1 (UniProt)
DCC:DIP13alpha ComplexREACT_23064 (Reactome)
DCC:DIP13alpha:

Caspase-9

ComplexREACT_22628 (Reactome)
Graf-2/

Arhgap10

ProteinA1A4S6 (UniProt)
NRAGE ProteinQ9Y5V3 (UniProt)
PAK-2p34:

RHG10 complex

ComplexREACT_14362 (Reactome)
Protease/caspase

cleaved UNC5A fragment bound to PM

ProteinQ6ZN44 (UniProt)
Protease/caspase

cleaved UNC5B fragment bound to PM

ProteinQ8IZJ1 (UniProt)
UNC5A ProteinQ6ZN44 (UniProt)
UNC5A fragment

with death domain

ProteinQ6ZN44 (UniProt)
UNC5A:NRAGE ComplexREACT_23063 (Reactome)
UNC5B ProteinQ8IZJ1 (UniProt)
UNC5B fragment

with death domain

ProteinQ8IZJ1 (UniProt)
Ubiquitin ligase REACT_4282 (Reactome)
Unc5B with death

domain:DAPK

ComplexREACT_23335 (Reactome)
active caspase-3 ComplexREACT_2467 (Reactome)
perinuclear PAK-

2p34:RHG10 complex

ComplexREACT_14389 (Reactome)
phospho-PAK-2p34

(Thr 402)

ProteinQ13177 (UniProt)
polyubiquitinated

PAK-2p34

ComplexREACT_13958 (Reactome)
ubiquitin ProteinREACT_3316 (Reactome)
ubiquitinated PAK-

2p34

ComplexREACT_14454 (Reactome)
unidentified caspase REACT_14138 (Reactome)

Annotated Interactions

No annotated interactions

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