USP17 deubiquitinates RCE1, CDC25A, DDX58, IFIH1

USP17 regulates cell proliferation by deubiquitinating and inhibiting RCE1, which influences the localization and activation of the small GTPases NRAS and HRAS (Burrows et al. 2009). In addition, USP17 mediates deubiquitination of CDC25A, which prevents CDC25A degradation by the proteasome during the G1/S and G2/M phases, promoting cell-cycle progression (Pereq et al. 2010). USP17 cleaves Lys-48 and Lys-63-linked polyubiquitin chains from the cytoplasmic innate immune receptors DDX58 (RIG-I) and IFIH1 (MDA5), which increases activation of the IFN-beta promoter, part of the cellular response to viral infection (Chen et al. 2010). USP17 expression is upregulated by interleukin-4 and interleukin-6 (Burrows et al. 2004).

USP17通过去泛素化和抑制RCE1来调节细胞增殖，RCE1影响小GTPase NRAS和HRAS的定位和激活（Burrows等，2009）。此外，USP17介导CDC25A的去泛素化，防止CDC25A在G1/S和G2/M期被蛋白酶体降解，从而促进细胞周期进程（Pereq等，2010）。USP17能够从细胞质中的先天免疫受体DDX58（RIG-I）和IFIH1（MDA5）上切割Lys-48和Lys-63连接的多泛素链，从而增加IFN-β启动子的激活，这是细胞对病毒感染响应的一部分（Chen等，2010）。USP17的表达受到白细胞介素-4和白细胞介素-6的诱导（Burrows等，2004）。