Advances in the study of structure,functions and inhibitors of deubiquitinating enzyme USP1
Ubiquitination is an essential post-translational modification for maintaining cell homeostasis.Ubiquitination is involved in the regulation of protein function,localization and transformation by linking ubiquitin to target proteins.The process of deubiquitization mediated by deubiquitinating enzymes is the reverse reaction of ubiquitination and participates in the recovery,editing and rearrangement of ubiquitin.Ubiquitin-specific proteases are the largest family of deubiquitinating enzymes,and ubiquitin-specific processing peptidase 1(USP1)is an important subtype of them.USP1 is widely involved in maintaining genome integrity,cell cycle and cell homeostasis.Abnormal expression of USP1 is found in multiple tumor types,so this target has received a lot of attention.At present,the small molecule USP1 inhibitor KSQ-4279 is the most advanced.It is in phase Ⅰ clinical trial.ISM3091 has also obtained the clinical trial approval in China and the United States,and clinical trials will be carried out soon.In this paper,the structure,regulation,physiological function of USP1,the relationship between USP1 and tumorigenesis and the inhibitors of USP1 are reviewed.
NETL
NSTL
万方数据
