Laboratory of Veterinary Physiology, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido 069-8501, Japan.
Int J Mol Sci. 2021 Jan 26;22(3):1209. doi: 10.3390/ijms22031209.
Ubiquitin specific protease (USP) 2 is a multifunctional deubiquitinating enzyme. USP2 modulates cell cycle progression, and therefore carcinogenesis, via the deubiquitination of cyclins and Aurora-A. Other tumorigenic molecules, including epidermal growth factor and fatty acid synthase, are also targets for USP2. USP2 additionally prevents p53 signaling. On the other hand, USP2 functions as a key component of the CLOCK/BMAL1 complex and participates in rhythmic gene expression in the suprachiasmatic nucleus and liver. USP2 variants influence energy metabolism by controlling hepatic gluconeogenesis, hepatic cholesterol uptake, adipose tissue inflammation, and subsequent systemic insulin sensitivity. USP2 also has the potential to promote surface expression of ion channels in renal and intestinal epithelial cells. In addition to modifying the production of cytokines in immune cells, USP2 also modulates the signaling molecules that are involved in cytokine signaling in the target cells. knockout mice exhibit changes in locomotion and male fertility, which suggest roles for USP2 in the central nervous system and male genital tract, respectively. In this review, we summarize the cellular events with USP2 contributions and list the signaling molecules that are upstream or downstream of USP2. Additionally, we describe phenotypic differences found in the in vitro and in vivo experimental models.
泛素特异性蛋白酶 (USP) 2 是一种多功能去泛素化酶。USP2 通过去泛素化细胞周期蛋白和 Aurora-A 来调节细胞周期进程，从而影响肿瘤发生。其他致癌分子，包括表皮生长因子和脂肪酸合酶，也是 USP2 的靶标。USP2 还可以防止 p53 信号转导。另一方面，USP2 作为 CLOCK/BMAL1 复合物的关键组成部分，参与了视交叉上核和肝脏中的节律基因表达。USP2 变体通过控制肝糖异生、肝胆固醇摄取、脂肪组织炎症以及随后的全身胰岛素敏感性来影响能量代谢。USP2 还有可能促进肾脏和肠道上皮细胞中离子通道的表面表达。除了调节免疫细胞中细胞因子的产生外，USP2 还调节细胞因子信号转导中涉及的信号分子。USP2 基因敲除小鼠表现出运动和雄性生育力的变化，这表明 USP2 在中枢神经系统和雄性生殖道中分别发挥作用。在这篇综述中，我们总结了具有 USP2 贡献的细胞事件，并列出了 USP2 上游或下游的信号分子。此外，我们还描述了在体外和体内实验模型中发现的表型差异。
