Anaphase-promoting complex/cyclosome-cdh1 mediates the ubiquitination and degradation of TRB3
Anaphase-promoting complex/cyclosome-cdh1 mediates the ubiquitination and degradation of TRB3
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DOI：
10.1016/j.bbrc.2009.12.175
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发表时间：
2010-02-12
影响因子：
3.1
通讯作者：
Hayashi, Hidetoshi
中科院分区：
文献类型：
--
作者：
Ohoka, Nobumichi;Sakai, Satoshi;Hayashi, Hidetoshi
我们最近证明了TRB3是一种新的内质网应激诱导蛋白，它是由CHOP和ATF4诱导的，以调节其功能和内质网应激诱导的细胞死亡，然而，对TRB3功能的调控尚未得到很好的描述。我们证明了TRB3是一种受泛素-蛋白酶体系统调节的不稳定蛋白质，TRB3的羧基末端结构域是蛋白质降解所必需的。在这个区域，我们发现了典型的D-box基序，这是依赖于后期促进复合体/环体(APC/C)的蛋白降解的关键序列。TRB3蛋白通过删除其D-box基序而稳定，并与APC/C共激活蛋白CDc20和CDH1相互作用。TRB3蛋白的表达水平受CDH1过表达的影响，但不受CDC20的影响。此外，CDH1的敲除增强了内源性TRB3的表达水平，并抑制了其泛素化水平。这些结果表明，APC/C-CDH1参与了TRB3蛋白的泛素化，并下调了TRB3蛋白(C)2010的稳定性。版权所有
We hive recently demonstrated that TRB3, a novel endoplasmic reticulum (ER) stress-inducible protein, is induced by CHOP and ATF4 to regulate their function and ER stress-induced cell death, however, the regulation of TRB3 function has not been well characterized Here we demonstrate that TRB3 is an unstable protein regulated by the ubiquitin-proteasome system The carboxyl-terminal domain of TRB3 is necessary for protein degradation. and in this region, we found the typical D-box motif, which is a critical sequence for the anaphase-promoting complex/cyclosome (APC/C) dependent proteolysis. TRB3 proteins were stabilized by deletion of its D-box motif and interacted with APC/C coactivator proteins, Cdc20 and Cdh1. The expression level of TRB3 protein is down-regulated by over-expression of Cdh1 but not by that of Cdc20 In addition, knockdown of Cdh1 enhanced the endogenous TRB3 expression level and suppressed Its ubiquitination level These results suggest that APC/C-Cdh1 is involved in ubiquitination and down-regulating the stability of TRB3 protein (C) 2010 Elsevier Inc. All rights reserved