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 FBW7α and abolishes FBW7α-mediated degradation of c-Myc. Furthermore, USP38 can restore the inhibitory effect of FBW7α on proliferation. Taken together, our study uncovers a novel role for USP38 in the regulation of c-Myc abundance and stability.

癌蛋白 c-Myc 是一种主转录因子，可调节与细胞周期、细胞生长和细胞代谢相关的大量基因的表达。因此，重要的是要控制 c-Myc 的水平。有许多蛋白质负责 c-Myc 的降解。然而，c-Myc 的去泛素化酶介导的稳定性仍然不太清楚。在这项研究中，我们发现 USP38，一种泛素特异性蛋白酶，调节 c-Myc 的水平和功能。USP38 可以抑制 c-Myc 的多泛素化，从而增加 c-Myc 的稳定性。在功能上，USP38 能够通过依赖 c-Myc 的方式促进细胞增殖。从机制上讲，USP38 与 FBW7α 发生物理相互作用并消除 FBW7α 介导的 c-Myc 降解。此外，USP38可以恢复FBW7α对增殖的抑制作用。总之，我们的研究揭示了 USP38 在调节 c-Myc 丰度和稳定性方面的新作用。