USP37 directly deubiquitinates and stabilizes c-Myc in lung cancer.
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| 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.
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| Authors | J Pan, Q Deng, C Jiang, X Wang, T Niu, H Li, T Chen, J Jin, W Pan, X Cai, X Yang, M Lu, J Xiao, P Wang |
| Journal | Oncogene (Oncogene) Vol. 34 Issue 30 Pg. 3957-67 (Jul 23 2015) ISSN: 1476-5594 [Electronic] England |
| PMID | 25284584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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