The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1.
Proapoptotic Bcl-2 family members, such as Bax, promote release of cytochrome c from mitochondria, leading to caspase activation and cell death. It was previously reported that modulator of apoptosis protein 1 (MOAP-1), an enhancer of Bax activation induced by DNA damage, is stabilized by Trim39, a protein of unknown function. ... In this paper, we show that MOAP-1 is a novel substrate of the anaphase-promoting complex (APC/C(Cdh1)) ubiquitin ligase. The influence of Trim39 on MOAP-1 levels stems from the ability of Trim39 (a RING domain E3 ligase) to directly inhibit APC/C(Cdh1)-mediated protein ubiquitylation. Accordingly, small interfering ribonucleic acid-mediated knockdown of Cdh1 stabilized MOAP-1, thereby enhancing etoposide-induced Bax activation and apoptosis. These data identify Trim39 as a novel APC/C regulator and provide an unexpected link between the APC/C and apoptotic regulation via MOAP-1.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Adenomatous Polyposis Coli Protein, Apoptosis, Apoptosis Regulatory Proteins, Blotting, Western, Cadherins, Carrier Proteins, DNA Damage, Flow Cytometry, G1 Phase, HeLa Cells, Humans, Immunoprecipitation, RNA, Small Interfering, Recombinant Proteins, Ubiquitin, Ubiquitination, bcl-2-Associated X Protein
Adaptor Proteins, Signal Transducing, Adenomatous Polyposis Coli Protein, Apoptosis, Apoptosis Regulatory Proteins, Blotting, Western, Cadherins, Carrier Proteins, DNA Damage, Flow Cytometry, G1 Phase, HeLa Cells, Humans, Immunoprecipitation, RNA, Small Interfering, Recombinant Proteins, Ubiquitin, Ubiquitination, bcl-2-Associated X Protein
J. Cell Biol.
Date: Apr. 30, 2012
PubMed ID: 22529100
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