STUB1 is essential for T-cell activation by ubiquitinating CARMA1
STUB1 is essential for T-cell activation by ubiquitinating CARMA1
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STUB1 通过泛素化 CARMA1 对于 T 细胞激活至关重要
DOI：
10.1002/eji.201242554
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发表时间：
2013-04-01
影响因子：
5.4
通讯作者：
Liu, Yu
中科院分区：
文献类型：
--
作者：
Wang, Shuai;Li, Yi;Liu, Yu
Ag受体结合通过激活包括NF-B在内的几种转录因子触发淋巴细胞活化和增殖。含有半胱天冬酶募集结构域（CARD）的膜相关鸟苷酸激酶（MAGUK）蛋白1（CARMA 1）是连接Ag受体与NF-B活化的必需衔接蛋白。在这里，我们确定了应激诱导磷蛋白1同源性和U盒蛋白1（STUB 1）作为CARMA 1相关蛋白。STUB 1与CARMA 1组成性相互作用，并且这种相互作用通过TCR刺激而增强。通过RNAi下调STUB 1表达显著减少了TCR诱导的典型NF-B活化和IL-2产生。此外，STUB 1的过表达增强了CARMA 1的泛素化，而STUB 1的敲低则消除了TCR刺激诱导的CARMA 1的内源性泛素化。随后，由STUB 1催化的CARMA 1的泛素化被鉴定为Lys-27连接，这对于CARMA 1介导的NF-B活化是重要的。这些数据提供了第一个证据，证明STUB 1对CARMA 1的泛素化促进了TCR诱导的NF-B信号传导。
Ag receptor engagement triggers lymphocyte activation and proliferation by activating several transcription factors including NF-B. Caspase recruitment domain (CARD) containing membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) is an essential adaptor protein that links Ag receptors to NF-B activation. Here, we identify stress-induced-phosphoprotein 1 homology and U-box containing protein 1 (STUB1) as a CARMA1-associated protein. STUB1 constitutively interacted with CARMA1, and the interaction was intensified by TCR stimulation. Downregulation of STUB1 expression by RNAi markedly diminished TCR-induced canonical NF-B activation and IL-2 production. Furthermore, overexpression of STUB1 enhanced the ubiquitination of CARMA1, whereas knockdown of STUB1 abolished the endogenous ubiquitination of CARMA1 induced by TCR stimulation. Subsequently, the ubiquitination of CARMA1 catalyzed by STUB1 was identified as Lys-27 linked, which is important for CARMA1-mediated NF-B activation. These data provide the first evidence that ubiquitination of CARMA1 by STUB1 promotes TCR-induced NF-B signaling.