Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors
Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors
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DOI：
10.1038/ni1066
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发表时间：
2004-05-01
影响因子：
30.5
通讯作者：
Ulevitch, RJ
中科院分区：
文献类型：
--
作者：
Chuang, TH;Ulevitch, RJ
Toll样受体（TLR）的激活导致对抗感染所需的促炎反应。因此，限制TLR信号传导对于防止保护性反应对宿主造成损伤是必不可少的。在这里，我们描述了一个环指蛋白，Triad3A，作为一个E3泛素蛋白连接酶，并增强泛素化和蛋白水解降解的一些TLR。Triad3A过表达促进了TLR4和TLR9的大量降解，伴随着信号转导的减少，但不影响TLR2的表达或信号转导。相反，通过小干扰RNA减少内源性Triad3A增加TLR表达并增强TLR活化。因此，Triad3A的泛素化代表了一种控制TLR信号传导的强度和持续时间的途径。
Activation of Toll-like receptors (TLRs) results in a proinflammatory response needed to combat infection. Thus, limiting TLR signaling is essential for preventing a protective response from causing injury to the host. Here we describe how a RING finger protein, Triad3A, acts as an E3 ubiquitin-protein ligase and enhances ubiquitination and proteolytic degradation of some TLRs. Triad3A overexpression promoted substantial degradation of TLR4 and TLR9 with a concomitant decrease in signaling, but did not affect TLR2 expression or signaling. Conversely, a reduction in endogenous Triad3A by small interfering RNA increased TLR expression and enhanced TLR activation. Thus, ubiquitination by Triad3A represents one pathway by which the intensity and duration of TLR signaling is controlled.