Besse Arnaud, Campos Alejandro D, Webster William K, Darnay Bryant G
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Box 143, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Biochem Biophys Res Commun. 2007 Aug 3;359(3):660-4. doi: 10.1016/j.bbrc.2007.05.149. Epub 2007 May 30.
TRAF-interacting protein (TRIP) was initially identified as a TRAF1- and TRAF2-binding partner that inhibited NF-kappaB activation without a known mechanism. Inspection of the TRIP sequence revealed an N-terminal RING domain, which is found in many E3 ubiquitin (Ub) ligases. We show that TRIP is a RING-dependent Ub ligase that undergoes auto-ubiquitination and requires an intact RING domain. Both TRIP and its RING mutant interact with TRAF1, 2, 3, 5, and 6, but failed to interact with CYLD and NIK. Stable expression of TRIP or a RING mutant did not affect IKK activation induced by TNF or IL-1 and had no affect on TNF-induced apoptosis. Similarly, RANKL-induced signaling and osteoclastogenesis were not affected by TRIP or its RING mutant. Interestingly, TRIP expression was down regulated during the late stages of osteoclastogenesis. Taken together, our results demonstrate that TRIP is a novel RING-dependent Ub ligase and a binding partner for TRAFs.
肿瘤坏死因子受体相关因子相互作用蛋白（TRIP）最初被鉴定为一种与TRAF1和TRAF2结合的蛋白，它可抑制核因子κB（NF-κB）激活，但作用机制不明。对TRIP序列的检查发现其N端存在一个RING结构域，该结构域存在于许多E3泛素（Ub）连接酶中。我们发现TRIP是一种依赖RING结构域的Ub连接酶，可发生自身泛素化，且需要完整的RING结构域。TRIP及其RING突变体均可与TRAF1、2、3、5和6相互作用，但不能与CYLD和NIK相互作用。稳定表达TRIP或其RING突变体不影响TNF或IL-1诱导的IKK激活，也不影响TNF诱导的细胞凋亡。同样，RANKL诱导的信号传导和破骨细胞生成不受TRIP或其RING突变体的影响。有趣的是，在破骨细胞生成后期TRIP表达下调。综上所述，我们的结果表明TRIP是一种新型的依赖RING结构域的Ub连接酶，也是TRAFs的结合蛋白。
