The covalent post-translational modification of proteins by ubiquitination not only influences protein stability and half-life, but also several aspects of protein function including enzymatic activity, sub-cellular localization, and interactions with binding partners. Protein ubiquitination status is determined by the action of large families of ubiquitin ligases and deubiquitinases, whose combined activities regulate many physiological and cellular pathways. The Ubiquitin Specific Protease (USP) family is one of 8 subfamilies of deubiquitinating enzymes composed of more than 50 members. Recent studies have shown that USP15 plays a critical role in regulating many aspects of immune and inflammatory function of leukocytes in response to a broad range of infectious and autoimmune insults and following tissue damage. USP15 regulated pathways reviewed herein include TLR signaling, RIG-I signaling, NF-kB, and IRF3/IRF7-dependent transcription for production of pro-inflammatory cytokines and type I interferons. In addition, USP15 has been found to regulate pathways implicated in tumor onset and progression such as p53, and TGF-β signaling, but also influences the leukocytes-determined immune and inflammatory microenvironment of tumors to affect progression and outcome. Hereby reviewed are recent studies of USP15 in model cell lines in vitro, and in mutant mice in vivo with reference to available human clinical datasets.

通过泛素化对蛋白质进行的共价翻译后修饰不仅影响蛋白质稳定性和半衰期，还影响蛋白质功能的几个方面，包括酶活性、亚细胞定位和与结合伙伴的相互作用。蛋白质泛素化状态由泛素连接酶和去泛素化酶大家族的作用决定，它们的联合活动调节许多生理和细胞通路。泛素特异性蛋白酶 (USP) 家族是由 50 多个成员组成的 8 个去泛素化酶亚家族之一。最近的研究表明，USP15 在调节白细胞免疫和炎症功能的许多方面起着关键作用，以应对广泛的感染和自身免疫损伤以及随后的组织损伤。审查的 USP15 调节通路包括 TLR 信号、RIG-I 信号、NF-kB 和 IRF3/IRF7 依赖性转录，用于产生促炎细胞因子和 I 型干扰素。此外，已发现 USP15 可调节与肿瘤发生和进展有关的通路，如 p53 和 TGF-β 信号，但也会影响白细胞决定的肿瘤免疫和炎症微环境，从而影响进展和结果。特此回顾了 USP15 在体外模型细胞系和体内突变小鼠中的最新研究，并参考了可用的人类临床数据集。已发现 USP15 可调节与肿瘤发生和进展有关的通路，如 p53 和 TGF-β 信号，但也会影响白细胞决定的肿瘤免疫和炎症微环境，从而影响进展和结果。特此回顾了 USP15 在体外模型细胞系和体内突变小鼠中的最新研究，并参考了可用的人类临床数据集。已发现 USP15 可调节与肿瘤发生和进展有关的通路，如 p53 和 TGF-β 信号，但也会影响白细胞决定的肿瘤免疫和炎症微环境，从而影响进展和结果。特此回顾了 USP15 在体外模型细胞系和体内突变小鼠中的最新研究，并参考了可用的人类临床数据集。