Anaphase-promoting complex/cyclosome-cdh1 mediates the ubiquitination and degradation of TRB3 |
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Authors: | Nobumichi Ohoka Satoshi Sakai Makoto Nakanishi |
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Institution: | a Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan b Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan |
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Abstract: | We have 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/CCdh1 is involved in ubiquitination and down-regulating the stability of TRB3 protein. |
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Keywords: | TRB3 APC/C Cdh1 Proteasome Degradation |
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