title: DUSP16 ablation arrests the cell cycle and induces cellular senescence.
abstract: Dual-specificity phosphatases (DUSPs) are a family of protein phosphatases that dephosphorylate both phosphotyrosine and phosphoserine/phosphothreonine residues. DUSPs are de-regulated in many human diseases, including cancers. However, the function of DUSPs in tumorigenesis remains largely unknown. Here, using short hairpin RNA-based gene knockdown, we found that several members of the DUSP family play critical roles in regulating cell proliferation. In particular, we showed that DUSP16 ablation leads to a G1/S transition arrest, reduced incorporation of 5-bromodeoxyuridine, enhanced senescence-associated β-galactosidase activity, and formation of senescence-associated heterochromatic foci. Mechanistically, DUSP16 silencing causes cellular senescence by activating the tumor suppressors p53 and Rb. The phosphatase activity of DUSP16 is necessary for antagonizing cellular senescence. Importantly, the expression levels of DUSP16 are up-regulated in human liver cancers, and are positively correlated with tumor cell proliferation. Taken together, our findings indicate that DUSP16 plays a role in tumorigenesis by protecting cancer cells from senescence.
authors.affiliation: Eastern Hepatobilliary Surgery Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Haibin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, China.|Center for Synthetic Biology Engineering Research, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Mu
authors.affiliation: Department of Cell Biology, Second Military Medical University, Shanghai, China.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academic of Sciences, China.
authors.forename: Lijian
authors.initials: L
authors.lastname: Hui
mesh_terms: D059447:Cell Cycle Checkpoints / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D054637:Dual-Specificity Phosphatases / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D020868:Gene Silencing; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054639:Mitogen-Activated Protein Kinase Phosphatases / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
chemical_list: D054639:Mitogen-Activated Protein Kinase Phosphatases; C439065:DUSP16 protein, human; D054637:Dual-Specificity Phosphatases
keywords: DUSP16; Rb; liver cancer; p53; senescence