Regulation of Apoptosis (Homo sapiens)

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14, 6224, 64, 93, 6, 7cytosolendosome membraneCaspase-3 precursorCleaved Caspase-9active caspase-3Protease/caspase cleaved UNC5A fragment bound to PMUNC5BGraf-2/ Arhgap10DCCunidentified caspaseubiquitinated PAK-2p34Protease/caspase cleaved UNC5B fragment bound to PMDAPKsATPphospho-PAK-2p34 (Thr 402)ADPDCC-interacting protein 13-alpha26S proteasomeUNC5ANRAGEPAK-2p34:RHG10 complexUNC5B fragment with death domainDCC's fragment with the ADD domainDCC:DIP13alphaperinuclear PAK-2p34:RHG10 complexUNC5A:NRAGEUNC5A fragment with death domainubiquitinpolyubiquitinated PAK-2p34DCC's inhibitory C-terminal domainUnc5B with death domain:DAPKUbiquitin ligaseDCC:DIP13alpha:Caspase-910855


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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  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


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External references


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NameTypeDatabase referenceComment


ComplexREACT_2353 (Reactome)
ADP Metabolite16761 (ChEBI)
ATP Metabolite15422 (ChEBI)


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)

protein 13-alpha

ProteinQ9UKG1 (UniProt)
DCC:DIP13alpha ComplexREACT_23064 (Reactome)


ComplexREACT_22628 (Reactome)


ProteinA1A4S6 (UniProt)
NRAGE ProteinQ9Y5V3 (UniProt)

RHG10 complex

ComplexREACT_14362 (Reactome)

cleaved UNC5A fragment bound to PM

ProteinQ6ZN44 (UniProt)

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


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

2p34:RHG10 complex

ComplexREACT_14389 (Reactome)

(Thr 402)

ProteinQ13177 (UniProt)


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


ComplexREACT_14454 (Reactome)
unidentified caspase REACT_14138 (Reactome)

Annotated Interactions

No annotated interactions

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