title: cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas.
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.
authors.affiliation: Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Shimin
authors.initials: S
authors.lastname: Hu
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Du
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Park
authors.forename: Allison
authors.initials: A
authors.lastname: Alcivar
authors.forename: Like
authors.initials: L
authors.lastname: Qu
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Gupta
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.forename: Mathijs
authors.initials: M
authors.lastname: Baens
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ye
authors.forename: Tae H
authors.initials: TH
authors.lastname: Lee
authors.forename: Peter
authors.initials: P
authors.lastname: Marynen
authors.forename: James L
authors.initials: JL
authors.lastname: Riley
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Yang
mesh_terms: D020169:Caspases; D002460:Cell Line; D016207:Cytokines / Q000276:immunology*; D050939:Gene Fusion; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014178:Translocation, Genetic
chemical_list: D016207:Cytokines; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein