Document Detail

TRIM32 protein sensitizes cells to tumor necrosis factor (TNFα)-induced apoptosis via its RING domain-dependent E3 ligase activity against X-linked inhibitor of apoptosis (XIAP).
MedLine Citation:
PMID:  21628460     Owner:  NLM     Status:  MEDLINE    
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 TNFα-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 TNFα-induced apoptosis by antagonizing XIAP, an anti-apoptotic downstream effector of TNFα signaling. This function may be associated with TRIM32-mediated tumor suppressive mechanism.
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:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-05-31
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  286     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-07-19     Completed Date:  2011-09-16     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  25729-38     Citation Subset:  IM    
Laboratory of Cell Signaling, Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 305-806, Korea.
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MeSH Terms
Apoptosis / drug effects*,  genetics
Base Sequence
Down-Regulation / drug effects
Gene Knockdown Techniques
HEK293 Cells
HeLa Cells
Proteasome Endopeptidase Complex / metabolism
RING Finger Domains*
Substrate Specificity
Transcription Factors / chemistry*,  deficiency,  genetics,  metabolism*
Tumor Necrosis Factor-alpha / pharmacology*
Ubiquitin-Protein Ligases / metabolism*
Ubiquitination / drug effects
X-Linked Inhibitor of Apoptosis Protein / metabolism*
Reg. No./Substance:
0/TRIM32 protein, human; 0/Transcription Factors; 0/Tumor Necrosis Factor-alpha; 0/X-Linked Inhibitor of Apoptosis Protein; EC Endopeptidase Complex; EC Ligases

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