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PMID: 16395405 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas.

The Journal of clinical investigation ·Vol. 116 ·No. 1 ·2006-01-00 ·Pages 174-81

Hu S, Du MQ, Park SM, Alcivar A, Qu L, Gupta S, Tang J, Baens M, Ye H, Lee TH, Marynen P, Riley JL, Yang X

Abstract

The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphomas is associated with independent chromosomal translocations that lead to the upregulation of either BCL10 or MALT1 or the generation of a fusion protein, cIAP2-MALT1. While both BCL10 and MALT1 are critically involved in antigen receptor-mediated NF-kappaB activation, the role of cIAP2 is not clear. Here we show that cIAP2 is a ubiquitin ligase (E3) of BCL10 and targets it for degradation, inhibiting antigen receptor-mediated cytokine production. cIAP2-MALT1 lacks E3 activity, and concomitantly, the BCL10 protein is stabilized in MALT lymphomas harboring this fusion. Furthermore, BCL10 and cIAP2-MALT1 synergistically activate NF-kappaB. These results reveal cIAP2 as an inhibitor of antigenic signaling and implicate its dysfunction in MALT lymphomas.

MeSH Terms
Caspases Cell Line Cytokines/immunology Gene Fusion Humans Inhibitor of Apoptosis Proteins/genetics,metabolism Lymphoma, B-Cell, Marginal Zone/enzymology,genetics,metabolism Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein Neoplasm Proteins/genetics,metabolism Recombinant Fusion Proteins/metabolism Translocation, Genetic
Chemicals
Cytokines Inhibitor of Apoptosis Proteins Neoplasm Proteins Recombinant Fusion Proteins Caspases MALT1 protein, human Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Hu Shimin
Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Du Ming-Qing
Park Sun-Mi
Alcivar Allison
Qu Like
Gupta Sanjeev
Tang Jun
Baens Mathijs
Ye Hongtao
Lee Tae H
Marynen Peter
Riley James L
Yang Xiaolu
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI25641
Published
2006-01-00
Pages
174-81
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC1323253
Subset
IM
Grants
NIAID NIH HHS · R01 AI057838 · United States
NIAID NIH HHS · AI057838 · United States
NIGMS NIH HHS · R01 GM060911 · United States
NIGMS NIH HHS · GM60911 · United States
NCI NIH HHS · R01 CA088868 · United States
NCI NIH HHS · CA88868 · United States
Corrections
CommentIn
PMID: 16395399
External Links
PubMed source DOI: 10.1172/JCI25641 PMC Full Text View journal details
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