The deubiquitinating enzyme USP17 regulates c‐Myc levels and controls cell proliferation and glycolysis
The deubiquitinating enzyme USP17 regulates c‐Myc levels and controls cell proliferation and glycolysis
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DOI：
10.1002/1873-3468.14296
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发表时间：
2022-01
期刊：
影响因子：
3.5
通讯作者：
M. Nagasaka;Yasumichi Inoue;Manaka Yoshida;Chiharu Miyajima;D. Morishita;Muneshige Tokugawa;Haruna Nakamoto;Mayumi Sugano;Nobumichi Ohoka;H. Hayashi
中科院分区：
文献类型：
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作者：
M. Nagasaka;Yasumichi Inoue;Manaka Yoshida;Chiharu Miyajima;D. Morishita;Muneshige Tokugawa;Haruna Nakamoto;Mayumi Sugano;Nobumichi Ohoka;H. Hayashi
c-Myc癌蛋白在人类癌症中经常过表达，对癌细胞增殖至关重要。泛素-蛋白酶体介导的降解失调是人类癌症中c-Myc表达上调的促成因素之一。我们在此将USP 17鉴定为一种新型的去泛素化酶，其调节c-Myc水平并控制细胞增殖和糖酵解。USP 17的过表达通过促进其去泛素化来稳定c-Myc蛋白。相反，USP 17的敲除促进了c-Myc降解并降低了c-Myc水平。USP 17的敲除还抑制细胞增殖和糖酵解。总的来说，目前的结果揭示了USP 17在调节c-Myc稳定性方面的新作用，并表明其作为癌症治疗靶点的潜力。
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.