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PMID:16395405

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Citation

Hu, S, Du, MQ, Park, SM, Alcivar, A, Qu, L, Gupta, S, Tang, J, Baens, M, Ye, H, Lee, TH, Marynen, P, Riley, JL and Yang, X (2006) cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas. J. Clin. Invest. 116:174-81

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.

Links

PubMed PMC1323253 Online version:10.1172/JCI25641

Keywords

Caspases; Cell Line; Cytokines/immunology; Gene Fusion; Humans; Inhibitor of Apoptosis Proteins/genetics; Inhibitor of Apoptosis Proteins/metabolism; Lymphoma, B-Cell, Marginal Zone/enzymology; Lymphoma, B-Cell, Marginal Zone/genetics; Lymphoma, B-Cell, Marginal Zone/metabolism; Neoplasm Proteins/genetics; Neoplasm Proteins/metabolism; Recombinant Fusion Proteins/metabolism; Translocation, Genetic

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:BIRC3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O95999

F

Seeded From UniProt

complete

HUMAN:BIRC3

enables

GO:0004842: ubiquitin-protein transferase activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:BCL10

enables

GO:0031625: ubiquitin protein ligase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13489

F

Seeded From UniProt

complete


See also

References

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