The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1.
Journal Article (Journal Article)
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.
Full Text
Duke Authors
Cited Authors
- Huang, N-J; Zhang, L; Tang, W; Chen, C; Yang, C-S; Kornbluth, S
Published Date
- April 2012
Published In
Volume / Issue
- 197 / 3
Start / End Page
- 361 - 367
PubMed ID
- 22529100
Pubmed Central ID
- PMC3341153
Electronic International Standard Serial Number (EISSN)
- 1540-8140
International Standard Serial Number (ISSN)
- 0021-9525
Digital Object Identifier (DOI)
- 10.1083/jcb.201111141
Language
- eng