title: 8-60hIPP5(m)-induced G2/M cell cycle arrest involves activation of ATM/p53/p21(cip1/waf1) pathways and delayed cyclin B1 nuclear translocation.
abstract: Protein phosphatase 1 (PP1) is a major serine/threonine phosphatase that controls gene expression and cell cycle progression. The active mutant IPP5 (8-60hIPP5(m)), the latest member of the inhibitory molecules for PP1, has been shown to inhibit the growth of human cervix carcinoma cells (HeLa). In order to elucidate the underlying mechanisms, the present study assessed overexpression of 8-60hIPP5(m) in HeLa cells. Flow cytometric and biochemical analyses showed that overexpression of 8-60hIPP5(m) induced G2/M-phase arrest, which was accompanied by the upregulation of cyclin B1 and phosphorylation of G2/M-phase proteins ATM, p53, p21(cip1/waf1) and Cdc2, suggesting that 8-60hIPP5(m) induces G2/M arrest through activation of the ATM/p53/p21(cip1/waf1)/Cdc2/ cyclin B1 pathways. We further showed that overexpression of 8-60hIPP5(m) led to delayed nuclear translocation of cyclin B1. 8-60hIPP5(m) also could translocate to the nucleus in G2/M phase and interact with pp1α and Cdc2 as demonstrated by co-precipitation assay. Taken together, our data demonstrate a novel role for 8-60hIPP5(m) in regulation of cell cycle in HeLa cells, possibly contributing to the development of new therapeutic strategies for cervix carcinoma.
authors.affiliation: Department of Biochemistry and Molecular Biology, Guangxi Medical University, Nanning, China E-mail : zengnn6@hotmail.com.
authors.forename: Qi-Yan
authors.initials: QY
authors.lastname: Zeng
authors.forename: Lin-Jie
authors.initials: LJ
authors.lastname: Zeng
authors.forename: Yu
authors.initials: Y
authors.lastname: Huang
authors.forename: Yong-Qi
authors.initials: YQ
authors.lastname: Huang
authors.forename: Qi-Fang
authors.initials: QF
authors.lastname: Zhu
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Liao
mesh_terms: D021581:Active Transport, Cell Nucleus; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D016203:CDC2 Protein Kinase; D002455:Cell Division / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000235:genetics; D056744:Cyclin B1 / Q000096:biosynthesis / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints / Q000235:genetics*; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors*; D021381:Protein Transport; D011506:Proteins / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: C534699:CCNB1 protein, human; D056744:Cyclin B1; D050759:Cyclin-Dependent Kinase Inhibitor p21; C547313:IPP5 protein, human; D011506:Proteins; D016159:Tumor Suppressor Protein p53; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; D054645:Protein Phosphatase 1