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Oncogene. 2017 Aug 24;36(34):4828-4842. doi: 10.1038/onc.2017.96. Epub 2017 Apr 10.

PIM1 induces cellular senescence through phosphorylation of UHRF1 at Ser311.

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Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
Department of Cadre Health Care, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Clinical Laboratory, Peking University First Hospital, Beijing, China.


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.

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