Regulation of apoptosis (Homo sapiens)
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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
Saving...Bibliography
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- Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF.; ''Inherited mitochondrial optic neuropathies.''; PubMed Europe PMC Scholia
- 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
- 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
- Jakobi R, McCarthy CC, Koeppel MA, Stringer DK.; ''Caspase-activated PAK-2 is regulated by subcellular targeting and proteasomal degradation.''; PubMed Europe PMC Scholia
- 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
- Yang Y, Yu X.; ''Regulation of apoptosis: the ubiquitous way.''; PubMed Europe PMC Scholia
- Voges D, Zwickl P, Baumeister W.; ''The 26S proteasome: a molecular machine designed for controlled proteolysis.''; PubMed Europe PMC Scholia
- 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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External references
DataNodes
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Annotated Interactions
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| Source | Target | Type | Database reference | Comment |
|---|---|---|---|---|
| 26S proteasome | mim-catalysis | R-HSA-211715 (Reactome)  | ||
| ARHGAP10 | R-HSA-211716 (Reactome) | |||
| K48polyUb-p-T402-PAK-2p43 | Arrow | R-HSA-211734 (Reactome) | ||
| K48polyUb-p-T402-PAK-2p43 | R-HSA-211715 (Reactome) | |||
| PAK-2p34:RHG10 complex | Arrow | R-HSA-211716 (Reactome) | ||
| PAK-2p34:RHG10 complex | R-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). | |||
| Ub | Arrow | R-HSA-211715 (Reactome) | ||
| Ub | R-HSA-211734 (Reactome) | |||
| Ubiquitin ligase | mim-catalysis | R-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 | Arrow | R-HSA-211731 (Reactome) |
