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	Regulation of Cidea protein stability by the ubiquitin-mediated proteasomal degradation pathway
	Chan, Siu Chiu ; Lin, Sheng-Cai ; Li, Peng
	2010-05-11 ; 2010-05-11
关键词	brown adipose tissue cell-death-inducing DNA-fragmentation-factor-45-like effector(CIDE) Cidea proteasome ubiquitin DNA-FRAGMENTATION-FACTOR BROWN ADIPOCYTES ENERGY-BALANCE BETA-CATENIN OBESITY DEATH APOPTOSIS LIGASE TRANSFORMATION THERMOGENESIS Biochemistry & Molecular Biology
中文摘要	Cidea, one of three members of the CIDE (cell-death-inducing DNA-fragmentation-factor-45-like effector) family of proteins, is highly enriched in brown adipose tissue, in which it plays a critical role in adaptive thermogenesis and fat accumulation. Cidea-mill mice have increased energy expenditure with resistance to high-fat-diet-induced obesity and diabetes. However, little is known as to how the Cidea protein is regulated. In the present study we show that Cidea is a short-lived protein as measured by cycloheximide-based protein chase experiments in different cell lines or in differentiated brown adipocytes. Proteasome inhibitors specifically increased the stability of both transfected and endogenous Cidea protein. Furthermore, Cidea protein was found to be polyubiquitinated when overexpressed in different culture cells as well as in differentiated mature brown adipocytes. Extensive mutational analysis of individual lysine residues revealed that ubiquitinated lysine residues are located in the N-terminal region of Cidea, as alteration of these lysine residues to alanine (N-5KA mutant) renders Cidea much more stable when compared with wild-type or C-terminal lysine-less mutant (C-5KA). Furthermore, K23 (Lys(23)) within the N-terminus of the Cidea was identified as the major contributor to its polyubiquitination signal and the protein instability. Taken together, the results of our study demonstrated that the ubiquitin-proteasome system confers an important post-translational modification that controls the protein stability of Cidea.
语种	英语 ; 英语
出版者	PORTLAND PRESS LTD ; LONDON ; THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND
内容类型	期刊论文
源URL	[http://hdl.handle.net/123456789/26739]
专题	清华大学
推荐引用方式 GB/T 7714	Chan, Siu Chiu,Lin, Sheng-Cai,Li, Peng. Regulation of Cidea protein stability by the ubiquitin-mediated proteasomal degradation pathway[J],2010, 2010.
APA	Chan, Siu Chiu,Lin, Sheng-Cai,&Li, Peng.(2010).Regulation of Cidea protein stability by the ubiquitin-mediated proteasomal degradation pathway..
MLA	Chan, Siu Chiu,et al."Regulation of Cidea protein stability by the ubiquitin-mediated proteasomal degradation pathway".(2010).

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