CIAP2 通过靶向 Bcl10 进行降解来抑制抗原受体信号传导。

CIAP2 inhibits anigen receptor signaling by targeting Bcl10 for degredation.

作者信息

Hu Shimin, Alcivar Allison, Qu Like, Tang Jun, Yang Xiaolu

机构信息

Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.

出版信息

Cell Cycle. 2006 Jul;5(13):1438-42. doi: 10.4161/cc.5.13.2866. Epub 2006 Jul 1.

DOI:10.4161/cc.5.13.2866

PMID:16775419

Abstract

The cellular inhibitor of apoptosis 2 (cIAP2) is a RING-containing protein ubiquitin ligase. In a high percentage of mucosa-associated lymphoid tissue (MALT) lymphomas, cIAP2 is fused to MALT1/paracaspase as a result of the t(11;18)(q21;q21) translocation. The physiological function of cIAP2 in lymphocytes and how this function may be affected by the translocation are not well understood. We have shown that cIAP2 normally inhibits antigen receptor signaling by mediating the ubiquitination and degradation of Bcl10, a critical component for antigenic signaling to NF-kappaB. The cIAP2-MALT1 fusion protein lacks this E3 activity and is incapable of ubiquitinating Bcl10, likely causing enhanced Bcl10 expression. Furthermore, cIAP2-MALT1 and Bcl10 synergistically activate NF-kappaB. These results reveal a physiological function of cIAP2, identify Bcl10 upregulation as a unifying molecular mechanism for MALT lymphomas, and define the mechanism and effects of this upregulation in t(11;18)-positive MALT lymphomas.

摘要

细胞凋亡抑制蛋白2（cIAP2）是一种含RING结构域的蛋白质泛素连接酶。在高比例的黏膜相关淋巴组织（MALT）淋巴瘤中，由于t(11;18)(q21;q21)易位，cIAP2与MALT1/副胱天蛋白酶融合。cIAP2在淋巴细胞中的生理功能以及这种功能如何受到易位的影响尚不清楚。我们已经表明，cIAP2通常通过介导Bcl10的泛素化和降解来抑制抗原受体信号传导，Bcl10是抗原信号传导至NF-κB的关键成分。cIAP2-MALT1融合蛋白缺乏这种E3活性，无法使Bcl1o泛素化，可能导致Bcl10表达增强。此外，cIAP2-MALT1和Bcl10协同激活NF-κB。这些结果揭示了cIAP2的生理功能，确定Bcl10上调是MALT淋巴瘤的统一分子机制，并明确了t(11;18)阳性MALT淋巴瘤中这种上调的机制和影响。