泛素化修饰是蛋白质翻译后修饰的主要类型之一。蛋白质可以通过泛素化修饰被多聚泛素链标记, 带有多聚泛素链的靶蛋白进一步被蛋白酶体识别并降解。泛素化及去泛素化是调节细胞周期进程的重要机制,细胞周期相关蛋白包括各种细胞周期蛋白(cyclin,CCN)、细胞周期蛋白依赖激酶(cyclin-dependent kinases, CDKs)和细胞周期蛋白依赖激酶抑制因子(cyclin-dependent kinase inhibitors, CKIs)等均可被泛素化修饰。近年来研究发现,去泛素化酶(deubiquitinating enzymes, DUBs)家族中的泛素特异性蛋白酶(ubiquitin-specific proteases, USPs)能够抑制肝癌进展。USPs可以逆转蛋白质的泛素化降解过程,影响肝癌细胞凋亡、自噬、肿瘤信号通路、细胞周期调控、DNA 损伤和化疗耐药等过程,进而影响肝癌的发生与发展。本文就去泛素化酶USPs家族调控肝癌细胞周期影响肝癌进程及在化疗耐药中作用的研究新进展进行综述, 以期为寻找新的肝癌药物治疗靶点提供参考路径。

Ubiquitination is one of the major types of protein post-translational modifications. Proteins can be labeled with polyubiquitin chains through ubiquitination, which enables their recognition and subsequent degradation by the proteasome. Ubiquitination and deubiquitination are essential mechanisms for regulating the cell cycle process. Cell cycle-associated proteins, including various cyclins (CCNs), cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CKIs), can all undergo ubiquitination. Recent studies have found that ubiquitin-specific proteases (USPs), members of the deubiquitinating enzyme (DUB) family, can inhibit the progression of liver cancer. USPs can reverse the ubiquitin-mediated degradation of proteins, thereby affecting apoptosis, autophagy, tumor signaling pathways, cell cycle regulation, DNA damage, and chemoresistance in liver cells, ultimately influencing the initiation and development of liver cancer. This article reviews recent research progress on the role of the DUB family member USPs in regulating the cell cycle of liver cancer cells, and their effects on tumor progression and chemoresistance, aiming to provide a reference for identifying new therapeutic targets for liver cancer treatment.