The deubiquitinase USP21 stabilizes MEK2 to promote tumor growth

摘要: Deubiquitinases (DUBs) play essential roles in normal cell proliferation and tumor growth. However, the molecular mechanisms of DUBs on hepatocellular carcinoma (HCC) remains largely unknown. In this study, based analysis several HCC datasets, we found that USP21 gene, which encodes a member ubiquitin-specific protease family, is highly amplified overexpressed HCCs, with extent up-regulation significantly correlating poor clinical outcomes. Inhibition lines decreased proliferation, anchorage-independent growth, cycle progression, vivo Conversely, ectopic expression transformed human hepatocyte line HL-7702 increased tumorigenicity MHCC97L. Mechanistically, stabilized MEK2 by decreasing its polyubiquitination at Lys48, thereby activating ERK signaling pathway. Importantly, partially mediated optimal USP21-mediated oncogenic phenotypes. These findings indicate deubiquitination stabilization critical role development.