cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas
cIAP2 is a ubiquitin protein ligase for BCL10 and is dysregulated in mucosa-associated lymphoid tissue lymphomas
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DOI：
10.1172/jci25641
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发表时间：
2006-01-01
影响因子：
15.9
通讯作者：
Yang, XL
中科院分区：
文献类型：
--
作者：
Hu, SM;Du, MQ;Yang, XL
粘膜相关淋巴组织（MALT）淋巴瘤的发病机制与独立的染色体易位有关，这些易位导致BCL 10或MALT 1上调或产生融合蛋白cIAP 2-MALT 1。尽管BCL 10和MALT 1都与抗原受体介导的NF-κ B活化密切相关，但cIAP 2的作用尚不清楚。在这里，我们表明，cIAP 2是一个泛素连接酶（E3）的BCL 10和目标降解，抑制抗原受体介导的细胞因子的产生。cIAP 2-MALT 1缺乏E3活性，并且伴随地，BCL 10蛋白在具有这种融合的MALT淋巴瘤中稳定。此外，BCL 10和cIAP 2-MALT 1协同激活NF-κ B。这些结果揭示cIAP 2作为抗原信号传导的抑制剂，并暗示其在MALT淋巴瘤中的功能障碍。
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-kappa B 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-kappa B. These results reveal cIAP2 as an inhibitor of antigenic signaling and implicate its dysfunction in MALT lymphomas.