Work

Preferential digestion of PCNA-ubiquitin and p53-ubiquitin linkages by USP7 to remove polyubiquitin chains from substrates

Year: 2019

Type: article

Abstract: Ubiquitin-specific protease 7 (USP7) regulates various cellular pathways through its deubiquitination activity. Despite the identification of a growing number of substrates of USP7, the molecular mechanism by which USP7 removes ubiquitin chains from polyubiquitinated substrates remains unexplored. The present study investigated the mechanism underlying the deubiquitination of Lys 63 -linked polyubiquitinated proliferating cell nuclear antigen (PCNA). Biochemical analyses demonstrated that USP7 efficiently removes polyubiquitin chains from polyubiquitinated PCNA by preferential cleavage of the PCNA-ubiquitin linkage. This property was largely attributed to the poor activity toward Lys 63 -linked ubiquitin chains. The preferential cleavage of substrate-ubiquitin linkages was also observed for Lys 48 -linked polyubiquitinated p53 because of the inefficient cleavage of the Lys 48 -linked ubiquitin chains. The present findings suggest a mechanism underlying the removal of polyubiquitin signals by USP7.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.ra118.005167

Authors: Yuji Masuda, Rie Kanao, Hidehiko Kawai, Iwao Kukimoto, Chikahide Masutani

Institutions: Research Institute of Environmental Medicine, Nagoya University, Nagoya University, Hiroshima University, National Institute of Infectious Diseases

Language: English

Topic: Ubiquitin and proteasome pathways

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: hybrid

Estimated APC paid: $3,430

Funders: Takeda Science Foundation, Ministry of Education, Culture, Sports, Science and Technology, National Institutes of Health, Japan Society for the Promotion of Science