去泛素化酶在肝癌发生发展中的研究进展

Research advances on deubiquitinating enzymes involved in the development of hepatocellular carcinoma

泛素-蛋白酶体途径(ubiquitin-proteasome pathway,UPP)是细胞内蛋白降解的重要调节系统。近年来的研究发现,去泛素化酶在肝癌中发挥重要作用。去泛素化酶可以逆转蛋白质泛素化降解过程,进而影响肿瘤的发生发展过程,包括凋亡和自噬、肿瘤的信号通路、细胞周期的调节和DNA损伤等。小分子抑制剂可以通过抑制去泛素化酶的功能起到抗肿瘤作用。本文对去泛素化酶在肝癌发生发展中的作用及特异性去泛素化酶小分子抑制剂进行综述,为寻找肝癌新的药物治疗靶点提供理论依据。

The ubiquitin-proteasome pathway is the primary regulator of intracellular protein degradation.In recent years,it has been found that multiple members of the deubiquitinating enzyme family play an important role in the development of liver cancer.The deubiquitinating enzymes remove ubiquitin chains of substrate proteins to maintain their stability;thus,they affect tumor progression via maintaining the stability of proteins involved in cell apoptosis,autophagy,cell cycle regulation,and DNA damage.Some small molecule inhibitors can exert an anti-tumor effect by inhibiting the activity of deubiquitinating enzymes.Here,we have reviewed research regarding deubiquitinating enzymes and their small molecule inhibitors in order to provide a new theoretical foundation for exploring novel and effective therapeutic targets for liver cancer.