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- Title
cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas.
- Authors
Shimin Hu; Ming-Qing Du; Sun-Mi Park; Alcivar, Allison; Like Qu; Gupta, Sanjeev; Jun Tang; Baens, Mathijs; Hongtao Ye; Lee, Tae H.; Marynen, Peter; Riley, James L.; Xiaolu Yang
- 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-B 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-B. These results reveal cIAP2 as an inhibitor of antigenic signaling and implicate its dysfunction in MALT lymphomas.
- Subjects
PROTEINS; LYMPHOMAS; LYMPHOID tissue; MUCOUS membranes; IMMUNE system; LIGASES
- Publication
Journal of Clinical Investigation, 2006, Vol 116, Issue 1, p174
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI25641