Journal
ONCOGENE
Volume 34, Issue 30, Pages 3957-3967Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2014.327
Keywords
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Funding
- National Basic Research Program of China (973 program) [2010CB529704, 2012CB910404]
- National Natural Science Foundation of China [30800587, 30971521, 31171338]
- Science and Technology Commission of Shanghai Municipality [11DZ2260300, 09QA1401900, 13QH1401]
- Doctoral Fund of Ministry of Education of China [20130076110022]
- Program for New Century Excellent Talents in University [NCET-10-0387]
- Dawn Program of Shanghai Education Commission [11SG27]
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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.
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