| Literature DB >> 27070702 |
Yibin Yang1, Priscilla Kelly1, Arthur L Shaffer1, Roland Schmitz1, Hee Min Yoo1, Xinyue Liu1, Da Wei Huang1, Daniel Webster1, Ryan M Young1, Masao Nakagawa1, Michele Ceribelli1, George W Wright2, Yandan Yang1, Hong Zhao1, Xin Yu1, Weihong Xu1, Wing C Chan3, Elaine S Jaffe4, Randy D Gascoyne5, Elias Campo6, Andreas Rosenwald7, German Ott8, Jan Delabie9, Lisa Rimsza10, Louis M Staudt11.
Abstract
Chronic active B cell receptor (BCR) signaling, a hallmark of the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), engages the CARD11-MALT1-BCL10 (CBM) adapter complex to activate IκB kinase (IKK) and the classical NF-κB pathway. Here we show that the CBM complex includes the E3 ubiquitin ligases cIAP1 and cIAP2, which are essential mediators of BCR-dependent NF-κB activity in ABC DLBCL. cIAP1/2 attach K63-linked polyubiquitin chains on themselves and on BCL10, resulting in the recruitment of IKK and the linear ubiquitin chain ligase LUBAC, which is essential for IKK activation. SMAC mimetics target cIAP1/2 for destruction, and consequently suppress NF-κB and selectively kill BCR-dependent ABC DLBCL lines, supporting their clinical evaluation in patients with ABC DLBCL.Entities:
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Year: 2016 PMID： 27070702 PMCID： PMC6026033 DOI： 10.1016/j.ccell.2016.03.006
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743