PPM1B depletion induces premature senescence in human IMR-90 fibroblasts

Jeong Hyeon Park*, Tracy K. Hale, Rebecca Jane Smith, Tian Yang

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)45-52
Number of pages8
JournalMechanisms of Ageing and Development
Issue number1
Publication statusPublished - Jun 2014
Externally publishedYes


  • Cellular senescence
  • MAPK
  • P38
  • P53
  • PP2C
  • PPM1B

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