脱泛素酶OTUD7B调控肿瘤微环境和肿瘤进程的分子机制

Molecular mechanisms of deubiquitinase OTUD7B in regulating tumor microenvironment and progression

泛素化(ubiquitination)是一种蛋白质翻译后修饰过程,泛素(ubiquitin)以共价连接的方式形成多聚泛素链并结合到靶蛋白赖氨酸(lysine,K)残基上,该过程由泛素激活酶(ubiquitin-activating enzymes,UBE,E1)、泛素结合酶(ubiquitin-conjugating enzymes,UCE,E2)和泛素连接酶(ubiquitin ligases,E3)顺序激活[1]。经典的泛素化调节方式是通过泛素-蛋白酶体系统(ubiquitin-proteasome system,UPS)介导蛋白质降解而实现对靶蛋白含量的精确调控[2-3]。随着人们对泛素化认识的不断深入,除了UPS介导的蛋白质降解和更新外,泛素化还可通过非降解机制调节细胞功能,如K63-和M1 (Met1)-多聚泛素链可形成细胞内反应的平台,参与激酶活化和细胞内信号转导[4-5]。泛素化是一个可逆的动态过程,受到E3和脱泛素酶(deubiquitinase,DUB)的共同调节[6]。OTUD7B(OTU domain-containing 7B)是一种多功能脱泛素酶,介导K11-、K48-和K63-多聚泛素链解离,在生长发育、免疫应答和恶性肿瘤等生理病理过程中发挥重要作用。

Ubiquitination and deubiquitination are important mechanisms for regulating cell signal transduction. They regulate target proteins precisely and participate in physiological and pathological processes such as growth, development, immune response and cancer. OTUD7B (OTU domain-containing 7B) is a deubiquitinase that hydrolyzes K11-, K48- and K63-linked polyubiquitin chains, regulates intracellular signal transduction and mediates cell survival and proliferation. The abnormal expression of OTUD7B in various malignant tumors affects tumor progression and immune microenvironment. Here, we reviewed OTUD7B-mediated cellular signal transduction and its role in malignant tumors, in order to provide clues for the discovery of new targets of anti-cancer therapy targeting ubiquitin system.