The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1.
J Cell Biol
; 197(3): 361-7, 2012 Apr 30.
Article
em En
| MEDLINE
| ID: mdl-22529100
ABSTRACT
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.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Proteínas de Transporte
/
Caderinas
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Proteína da Polipose Adenomatosa do Colo
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Ubiquitina
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Proteínas Adaptadoras de Transdução de Sinal
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Proteínas Reguladoras de Apoptose
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Proteína X Associada a bcl-2
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Cell Biol
Ano de publicação:
2012
Tipo de documento:
Article