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

Shimin Hu, Ming Qing Du, Sun Mi Park, Allison Alcivar, Like Qu, Sanjeev Gupta, Jun Tang, Mathijs Baens, Hongtao Ye, Tae H. Lee, Peter Marynen, James L. Riley, Xiaolu Yang

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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-κB 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-κB. These results reveal cIAP2 as an inhibitor of antigenic signaling and implicate its dysfunction in MALT lymphomas.

Original languageEnglish
Pages (from-to)174-181
Number of pages8
JournalJournal of Clinical Investigation
Volume116
Issue number1
DOIs
Publication statusPublished - 2006 Jan 1

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All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Hu, S., Du, M. Q., Park, S. M., Alcivar, A., Qu, L., Gupta, S., Tang, J., Baens, M., Ye, H., Lee, T. H., Marynen, P., Riley, J. L., & Yang, X. (2006). cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas. Journal of Clinical Investigation, 116(1), 174-181. https://doi.org/10.1172/JCI25641