The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1.

dc.contributor.author

Huang, Nai-Jia

dc.contributor.author

Zhang, Liguo

dc.contributor.author

Tang, Wanli

dc.contributor.author

Chen, Chen

dc.contributor.author

Yang, Chih-Sheng

dc.contributor.author

Kornbluth, Sally

dc.coverage.spatial

United States

dc.date.accessioned

2014-03-06T16:00:39Z

dc.date.issued

2012-04-30

dc.description.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.

dc.identifier

http://www.ncbi.nlm.nih.gov/pubmed/22529100

dc.identifier

jcb.201111141

dc.identifier.eissn

1540-8140

dc.identifier.uri

https://hdl.handle.net/10161/8382

dc.language

eng

dc.publisher

Rockefeller University Press

dc.relation.ispartof

J Cell Biol

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10.1083/jcb.201111141

dc.subject

Adaptor Proteins, Signal Transducing

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Adenomatous Polyposis Coli Protein

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Apoptosis

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Apoptosis Regulatory Proteins

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Blotting, Western

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Cadherins

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Carrier Proteins

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DNA Damage

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Flow Cytometry

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G1 Phase

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HeLa Cells

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Humans

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Immunoprecipitation

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RNA, Small Interfering

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Recombinant Proteins

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Ubiquitin

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Ubiquitination

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bcl-2-Associated X Protein

dc.title

The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1.

dc.type

Journal article

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/22529100

pubs.begin-page

361

pubs.end-page

367

pubs.issue

3

pubs.organisational-group

Basic Science Departments

pubs.organisational-group

Duke

pubs.organisational-group

Duke Cancer Institute

pubs.organisational-group

Institutes and Centers

pubs.organisational-group

Pharmacology & Cancer Biology

pubs.organisational-group

School of Medicine

pubs.publication-status

Published

pubs.volume

197

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