Regulation of the deubiquitinating enzyme CYLD by IκB kinase gamma-dependent phosphorylation
Regulation of the deubiquitinating enzyme CYLD by IκB kinase gamma-dependent phosphorylation
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DOI：
10.1128/mcb.25.10.3886-3895.2005
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发表时间：
2005-05-01
影响因子：
5.3
通讯作者：
Sun, SC
中科院分区：
文献类型：
--
作者：
Reiley, W;Zhang, MY;Sun, SC
肿瘤抑制因子CYLD是一种去泛素化酶（DUB），可抑制关键信号分子的泛素化，包括肿瘤坏死因子（TNF）受体相关因子2 （TRA-F2）。然而，如何调节CYLD的功能仍是未知的。我们提供的证据表明，诱导磷酸化的CYLD是其调控的一个重要机制。在正常情况下，CYLD主要抑制TRAF2的泛素化。在对细胞刺激的反应中，CYLD经历了快速和短暂的磷酸化，这是信号诱导TRAF2泛素化和下游信号事件激活所必需的。有趣的是，CYLD磷酸化需要ikappa B激酶γ (IKK γ)，并且可以由IKK催化亚基诱导。这些发现表明CYLD是IKK的新靶点，CYLD的位点特异性磷酸化调节其信号功能。
Tumor suppressor CYLD is a deubiquitinating enzyme (DUB) that inhibits the ubiquitination of key signaling molecules, including tumor necrosis factor (TNF) receptor-associated factor 2 (TRA-F2). However, how the function of CYLD is regulated remains unknown. Here we provide evidence that inducible phosphorylation of CYLD is an important mechanism of its regulation. Under normal conditions, CYLD dominantly suppresses the ubiquitination of TRAF2. In response to cellular stimuli, CYLD undergoes rapid and transient phosphorylation, which is required for signal-induced TRAF2 ubiquitination and activation of downstream signaling events. Interestingly, the CYLD phosphorylation requires I kappa B kinase gamma (IKK gamma) and can be induced by IKK catalytic subunits. These findings suggest that CYLD serves as a novel target of IKK and that the site-specific phosphorylation of CYLD regulates its signaling function.