title: USP37 directly deubiquitinates and stabilizes c-Myc in lung cancer.
abstract: The oncoprotein c-Myc is frequently overexpressed in many cancers and is essential for cancer cell proliferation. Ubiquitin-proteasome-dependent degradation is one of the main ways in which cells control c-Myc abundance at a post-translational level. However, the underlying mechanism by which c-Myc is directly deubiquitinated is not fully understood. In this study, by screening ubiquitin-specific proteases (USPs) that may regulate c-Myc stability, we identified USP37 as a novel deubiquitinating enzyme (DUB) that stabilizes c-Myc via direct binding. The overexpression of USP37 markedly increases c-Myc abundance by blocking its degradation, whereas the depletion of USP37 promotes c-Myc degradation and reduces c-Myc levels. Further studies indicate that USP37 directly interacts with c-Myc and deubiquitinates c-Myc in a DUB activity-dependent manner. Functionally, USP37 regulates cell proliferation and the Warburg effect by regulating c-Myc levels. Clinically, USP37 is significantly upregulated in human lung cancer tissues, where its expression is positively correlated with c-Myc protein expression. Thus, our findings uncover a previously unrecognized role for USP37 in the regulation of c-Myc stability in lung cancer and suggest that USP37 might be a potential therapeutic target for the treatment of lung cancer.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Deng
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: C
authors.initials: C
authors.lastname: Jiang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: T
authors.initials: T
authors.lastname: Niu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: T
authors.initials: T
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: J
authors.initials: J
authors.lastname: Jin
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: W
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Central Laboratory, Shanghai 10th People's Hospital, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: M
authors.initials: M
authors.lastname: Lu
authors.affiliation: Department of Orthopedic Oncology, Changzheng Hospital, The Second Military Medical University, Shanghai, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Xiao
authors.affiliation: 1] Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China [2] Department of Central Laboratory, Shanghai 10th People's Hospital, School of Life Science and Technology, Tongji University, Shanghai, China.
authors.forename: P
authors.initials: P
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology*; D049109:Cell Proliferation; D010450:Endopeptidases / Q000502:physiology*; D006019:Glycolysis; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology*; D055550:Protein Stability; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D010450:Endopeptidases; C559980:USP37 protein, human