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 recognition 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.
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Research Article|
October 02 2015
The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights
Yi Wen;
Yi Wen
1
*Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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Li Shi;
Li Shi
1
*Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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Yiluan Ding;
Yiluan Ding
*Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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Rong Cui;
Rong Cui
*Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
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Wen-tian He;
Wen-tian He
†State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
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Hong-yu Hu;
Hong-yu Hu
2
†State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
2Correspondence may be addressed to either of these authors (email hyhu@sibcb.ac.cn or nxzhang@mail.shcnc.ac.cn).
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Naixia Zhang
Naixia Zhang
2
*Department of Analytical Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China
2Correspondence may be addressed to either of these authors (email hyhu@sibcb.ac.cn or nxzhang@mail.shcnc.ac.cn).
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Publisher: Portland Press Ltd
Received:
January 21 2015
Revision Received:
August 11 2015
Accepted:
August 12 2015
Accepted Manuscript online:
August 12 2015
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2015 Authors; published by Portland Press Limited
2015
Biochem J (2015) 471 (2): 155–165.
Article history
Received:
January 21 2015
Revision Received:
August 11 2015
Accepted:
August 12 2015
Accepted Manuscript online:
August 12 2015
Citation
Yi Wen, Li Shi, Yiluan Ding, Rong Cui, Wen-tian He, Hong-yu Hu, Naixia Zhang; The N-terminal ubiquitin-binding region of ubiquitin-specific protease 28 modulates its deubiquitination function: NMR structural and mechanistic insights. Biochem J 15 October 2015; 471 (2): 155–165. doi: https://doi.org/10.1042/BJ20150088
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