Regulation Of PTEN Stability By Deubiquitination Enzymes

PTEN stands for phosphatase and tension homologue deleted from chromosome 10,which is located on chromosome 10q23.3. Its encoded protein contains 403 amino acids, and its molecular weight is about 56kDa. PTEN’s structure includes three functional areas:an amino-terminal phosphatase domain, a C2 lipid binding region and the carboxy-terminal region consists of about 50 amino acids.PTEN protein show a double-specific phosphatase activity, lipid phosphatase and protein phosphataseactivity specifically minuses the phosphatidylinositol-3,4,5-triphosphate (PEP3)-position of the phosphate group, thereby antagonizing PI3K kinases,especially the inhibition of PI3K downstream AKT signal transduction pathway,further inhibits cell growth, proliferation, migration and so on.So it is an important tumor suppressor gene.In recent years, PTEN deletion or mutation have been found in a variety of tumors,we also know that hbmozygous deletion of the PTEN gene can lead to death when in mouse embryo,and heterozygous deletion of PTEN gene in mice can lead to many types of tumors,so PTEN is indeed confirmed a tumor suppressor in vivo.Given the importance of PTEN, its activity and stability will be subject to strict regulation. PTEN has a relatively long half-life and a higher endogenous protein level.In theory, the ubiquitination degradation and deubiquitination can balance the amount of protein and protein stability in addition to being influenced by transcription and protein synthesis.Up to now, the E3 of PTEN have been reported that NEDD4-1, WWP2, CHIP,XIAP and TRIM27/RFP,while DUB promoting PTEN deubiquitinase are the HAUSP/ USP7 and USP13.However,the former HAUSP/USP7 removes only monoubiquitination from PTEN,prompting PTEN transferring from the nucleus to the cytoplasmic, but does not effect the stability of PTEN protein and protein content. USP13 has been reported a polyubiquitination for PTEN,which protects PTEN from be degrated in cytoplasmic,Conserdering the importance of PTEN,there must be more DUBs for PTEN stablity,In the process, We found out USP10(a member of USPs family) who is able to maintain the connection with PTEN.About USP10 reports that it maintains the important appropriate cellular p53 protein level by resistance MDM2.In additional, article reported that p53 has a effect on PTEN in transcription,in turn PTEN effects p53 in protein level, whether USP10 effect on PTEN directly in protein or not has not been reported,so we provided proof to display the connection between of them.We found that USP10 has a obvious effective on PTEN by a series of experiments.In general,USP10 can remove the specific polyubiquitin chains of PTEN and inhibit the degradation of PTEN.So we hypothesize that USP10 is a other DUB for PTEN and it likely acts as a tumor suppressor by maintaining the level of PTEN.