The deubiquitinating enzyme USP17 regulates c‐Myc levels and controls cell proliferation and glycolysis
Mai Nagasaka, Yasumichi Inoue, Manaka Yoshida, Chiharu Miyajima, Daisuke Morishita, Muneshige Tokugawa, Haruna Nakamoto, Mayumi Sugano, Nobumichi Ohoka, Hidetoshi Hayashi
Abstract
The c-Myc oncoprotein is frequently overexpressed in human cancers and is essential for cancer cell proliferation. The dysregulation of ubiquitin-proteasome-mediated degradation is one of the contributing factors to the upregulated expression of c-Myc in human cancers. We herein identified USP17 as a novel deubiquitinating enzyme that regulates c-Myc levels and controls cell proliferation and glycolysis. The overexpression of USP17 stabilized the c-Myc protein by promoting its deubiquitination. In contrast, the knockdown of USP17 promoted c-Myc degradation and reduced c-Myc levels. The knockdown of USP17 also suppressed cell proliferation and glycolysis. Collectively, the present results reveal a novel role for USP17 in the regulation of c-Myc stability and suggest its potential as a therapeutic target for cancer treatment.