| TRIM32 sensitizes cells to TNF{alpha}-induced apoptosis via its RING domain-dependent E3 ligase activity against XIAP. | |
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MedLine Citation:
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PMID: 21628460 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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TRIM32, which belongs to the tripartite motif (TRIM) protein family, has the RING finger, B-box, and coiled-coil domain structures common to this protein family, along with an additional NHL domain at the C-terminus. TRIM32 reportedly functions as an E3 ligase for actin, a protein inhibitor of activated STAT y (PIASy), dysbindin and c-Myc, and it has been associated with diseases such as muscular dystrophy and epithelial carcinogenesis. Here, we identify a new substrate of TRIM32 and propose a mechanism through which TRIM32 might regulate apoptosis. Our overexpression and knockdown experiments demonstrate that TRIM32 sensitizes cells to TNFa-induced apoptosis. The RING domain is necessary for this pro-apoptotic function of TRM32 as well as being responsible for its E3 ligase activity. TRIM32 colocalizes and directly interacts with X-linked inhibitor of apoptosis (XIAP), a well-known cancer therapeutic target, through its coiled-coil and NHL domains. TRIM32 overexpression enhances XIAP ubiquitination and subsequent proteasome-mediated degradation, whereas TRIM32 knockdown has the opposite effect, indicating that XIAP is a substrate of TRIM32. In vitro reconstitution assay reveals that XIAP is directly ubiquitinated by TRIM32. Our novel results collectively suggest that TRIM32 sensitizes TNFa-induced apoptosis by antagonizing XIAP, an anti-apoptotic downstream effector of TNFa signaling. This function may be associated with TRIM32-mediated tumor suppressive mechanism. |
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Authors:
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Yeung Sook Ryu; Younglang Lee; Keun Woo Lee; Chae Young Hwang; Jin-Soo Maeng; Jeong-Hoon Kim; Yeon-Soo Seo; Kwan-Hee You; Byeongwoon Song; Ki-Sun Kwon |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-31 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-6-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Korea Research Institute of Bioscience and Biotechnology, Korea, Republic of; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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