The deubiquitinase USP38 promotes cell proliferation through stabilizing c-Myc

The oncoprotein c-Myc is a master transcription factor that regulates the expression of a large number of genes involved in cell cycle, cell growth, and cell metabolism. Hence, it is important to keep the level of c-Myc under control. There are many proteins responsible for the degradation of c-Myc. However, the deubiquitinase-mediated stabilization of c-Myc remains less well understood. In this study, we found that USP38, an ubiquitin-specific protease, regulates the levels and function of c-Myc. USP38 can inhibit the polyubiquitination of c-Myc, thereby increasing c-Myc stability. Functionally, USP38 is able to promote cell proliferation via a c-Myc dependent manner. Mechanistically, USP38 physically interacts with FBW7 alpha and abolishes FBW7 alpha-mediated degradation of c-Myc. Furthermore, USP38 can restore the inhibitory effect of FBW7 alpha on proliferation. Taken together, our study uncovers a novel role for USP38 in the regulation of c-Myc abundance and stability.