title: PIM1 induces cellular senescence through phosphorylation of UHRF1 at Ser311.
abstract: PIM1 is a proto-oncogene, encoding a serine/threonine protein kinase that regulates cell proliferation, survival, differentiation and apoptosis. Previous reports suggest that overexpression of PIM1 can induce cellular senescence. However, the molecular mechanism underlying this process is not fully understood. Here we report that UHRF1 is a novel substrate of PIM1 kinase, which could be phosphorylated at Ser311 and therefore promoted to degradation. Our data demonstrates that PIM1 destabilizes UHRF1, leading to DNA hypomethylation, which consequently results in genomic instability, increased p16 expression and subsequent induction of cellular senescence. Taken together, our results suggest that down-regulation of UHRF1 is an important mechanism of PIM1-mediated cellular senescence.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: K
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Cadre Health Care, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, Peking University First Hospital, Beijing, China.
authors.forename: B
authors.initials: B
authors.lastname: Jin
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhan
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Shen
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: W
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Mao
mesh_terms: D017209:Apoptosis / Q000502:physiology; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D019175:DNA Methylation / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D042822:Genomic Instability / Q000502:physiology; D006801:Humans; D010766:Phosphorylation / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D051573:Proto-Oncogene Proteins c-pim-1 / Q000378:metabolism*; D011519:Proto-Oncogenes / Q000502:physiology; D044767:Ubiquitin-Protein Ligases
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; C496634:PIM1 protein, human; D017346:Protein Serine-Threonine Kinases; D051573:Proto-Oncogene Proteins c-pim-1