The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights

doi:10.1042/BJ20150088

	The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights
	Wen, Yi 2; Shi, Li 2; Ding, Yiluan 2; Cui, Rong 2; He, Wen-tian 1; Hu, Hong-yu 1; Zhang, Naixia2
刊名	BIOCHEMICAL JOURNAL
	2015-10-15
卷号	471 页码:155-165
关键词	deubiquitinase NMR solution structure ubiquitin-binding region Usp28
ISSN号	0264-6021
DOI	10.1042/BJ20150088
文献子类	Article
英文摘要	The deubiquitinase ubiquitin-specific protease 28 (Usp28) contains a ubiquitin-binding region (UBR) composed of one ubiquitin-associated domain (UBA) and one ubiquitin-interacting motif (UIM) at its N-terminus. It is of interest that an additional small ubiquitin-like modifier (SUMO)-interacting motif (SIM) is located next to its UIM. To date, the functional role of the Usp28 UBR is still not understood. To elucidate the regulatory mechanism of the UBR on the full functional display of Usp28, in the present study, NMR and biochemical approaches were applied. The solution structure of Usp28 UBR was obtained, and the key residues responsible for ubiquitin and SUMO1/2 ecognition were identified. In addition, we find that the ubiquitin-binding ability of Usp28 UBR was required for full enzymatic activity of Usp28, whereas binding of SUMO1/2 impaired the catalytic activity of the enzyme by competitively blocking its interactions with ubiquitin substrates. Our findings provide a first insight into understanding how the enzymatic activity of Usp28 is regulated by its non-catalytic UBR and endogenous ligands.
资助项目	National Natural Science Foundation of China[21272246] ; National Natural Science Foundation of China[31300608] ; National Natural Science Foundation of China[31270773] ; Chinese Academy of Sciences[00000000] ; National Key Basic Research Program of China[2013CB910900]
WOS关键词	MOLECULAR-STRUCTURE DETERMINATION ; CHEMICAL-SHIFT INDEX ; DNA-DAMAGE-RESPONSE ; SUBSTRATE-SPECIFICITY ; SECONDARY STRUCTURE ; EMERGING ROLES ; XPLOR-NIH ; CANCER ; USP28 ; ENZYME
WOS研究方向	Biochemistry & Molecular Biology
语种	英语
出版者	PORTLAND PRESS LTD
WOS记录号	WOS:000369169000002
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276360]
专题	分析化学研究室
通讯作者	Hu, Hong-yu
作者单位	1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, Shanghai, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, Shanghai 200031, Peoples R China;
推荐引用方式 GB/T 7714	Wen, Yi,Shi, Li,Ding, Yiluan,et al. The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights[J]. BIOCHEMICAL JOURNAL,2015,471:155-165.
APA	Wen, Yi.,Shi, Li.,Ding, Yiluan.,Cui, Rong.,He, Wen-tian.,...&Zhang, Naixia.(2015).The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights.BIOCHEMICAL JOURNAL,471,155-165.
MLA	Wen, Yi,et al."The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights".BIOCHEMICAL JOURNAL 471(2015):155-165.