title: PPM1B depletion induces premature senescence in human IMR-90 fibroblasts.
abstract: p53 and NF-κB are key transcription factors in regulating the gene expression program of cellular and organismal senescence. PPM1B is a member of the protein phosphatase 2C family and plays a role in negatively regulating p53 and NF-κB thereby possibly attenuating the gene expression program of cellular senescence. Here, possible involvement of PPM1B in replicative senescence has been investigated using the in vitro aging model of IMR-90 cells. PPM1B protein levels are progressively decreased in a replicative age-dependent manner. Importantly, PPM1B depletion induces a robust senescence phenotype as evidenced by significant growth arrest and senescence marker expression. Given that PPM1B depletion-induced senescence is partially rescued by inactivating p38 MAPK, our results identify PPM1B as a critical regulator of both p38 MAPK-dependent and independent senescence pathways during normal cellular aging process.
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand. Electronic address: J.Park@massey.ac.nz.
authors.forename: Jeong Hyeon
authors.initials: JH
authors.lastname: Park
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Tracy K
authors.initials: TK
authors.lastname: Hale
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Rebecca Jane
authors.initials: RJ
authors.lastname: Smith
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Tian
authors.initials: T
authors.lastname: Yang
mesh_terms: D049109:Cell Proliferation / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000235:genetics*; D005347:Fibroblasts; D005786:Gene Expression Regulation; D006801:Humans; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000235:genetics*; D000071636:Protein Phosphatase 2C; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D048051:p38 Mitogen-Activated Protein Kinases; C000607456:PPM1A protein, human; C000607457:PPM1B protein, human; C000607460:PPM1G protein, human; D010749:Phosphoprotein Phosphatases; D000071636:Protein Phosphatase 2C
keywords: Cellular senescence; MAPK; PP2C; PPM1B; p38; p53