RESUMO
Ubiquitin-specific protease 14 (USP14), a member of the ubiquitin-specific proteases family, plays an important role in the development and progression of malignant tumors through removing ubiquitin chain from substrates such as androgen receptor (AR), cell cycle-related proteins and apoptosis-related proteins to regulate protein stability and activity. The mechanisms of USP14 in a variety of malignant tumors are complex and diverse, including promotion in cell proliferation and inflammation as well as inhibition in apoptosis, autophagy, and drug resistance. Simultaneously, aberrant expression of USP14 is closely correlated with poor prognosis in most malignant tumors. Therefore, USP14 is a potential drug target for tumor therapy, and the development of its inhibitors appears as a new direction of anti-tumor drug research. Currently, specific inhibitors of USP14 mainly include IU1, its analogs (IU1-47, IU1-206, IU1-248), and b-AP15. The inhibitory ability of IU1 analogs on USP14 activity is 10 times than that of IU1, due to the difference in crystal structure. On the other hand, the inhibitors of USP14 show powerful anti-tumor effects inducing tumor cell death through a variety of signal pathways, which enables the inhibitor as potential targeted drugs. It will be extremely important to further explore the relationship between USP14 and its inhibitors in the tumor development and progression. This review summarizes the latest research of USP14 and its inhibitors, including their structures and functions in malignant tumors. Furthermore, the problems, challenges, new directions and strategies for future research, were also reviewed in current study.
