| The tumor suppressor protein p53 has a variety of roles in responses to various stress signals.In such responses,p53 activates specific transcriptional targets that control cell cycle arrest,DNA repair,angiogenesis,autophagy,metabolism,migration,aging,senescence,and apoptosis.Since p53 has been identified as the most frequently altered gene in human cancers,regulation and stabilization of its normal functions are important.Stability of p53 is regulated by the ubiquitin-proteasome pathway(UPP),the expression of p53 protein was maintained at a low level under physiological conditions.Under stress conditions,the expression of P53 protein was up-regulated due to the inhibition of the degradation process of ubiquitin.Furthermore,it is readjusted by deubiquitination via deubiquitinating enzymes(DUBs)that can eliminate ubiquitin from p53.Diverse DUBs directly or indirectly affect the ubiquitination of p53 and,consequently,regulate various cellular processes associated with p53.As maintenance of p53 is regulated by a variety of DUBs,the interaction of DUBs and p53 can affect diseases such as cancer.Currently,DUBs have a central role in our understanding of various cancers,and some have potential in the development of effective therapeutic strategies.USP30,a member of the ubiquitin-specific protease family,is a novel mitochondrial deubiquitinating enzyme.USP30 includes a mitochondrial intermembrane part,a single transmembrane helix and a cytoplasmic catalytic domain.Recently,accumulating evidence has highlighted the important function of DUB3 in multiple cellular processes and diseases.USP30 antagonizes mitophagy driven by the ubiquitin ligase PARK2 and protein kinase PINK1,which are encoded by two genes associated with Parkinson’s disease.USP30 can deubiquitylate and stabilize dynamin-related protein 1(DRP1),thereby facilitating regulation of mitochondrial morphology,lipid metabolism,and hepatocarcinogenesis.Using a luciferase reporter screen,we found that overexpression of USP30 could significantly activate the DNA damage response signaling pathway.To better understand the regulation of p53,we tested the interaction between p53 and USP30 using co-immunoprecipitation.The results show that USP30,an ubiquitinspecific protease,forms specific complexes with p53 and stabilizes p53 by deubiquitinating it.In conclusion,these findings reveal that USP30 is a novel regulator of p53 stability and activity. |
