PPM1B depletion induces premature senescence in human IMR-90 fibroblasts

Mech Ageing Dev. 2014 Jun:138:45-52. doi: 10.1016/j.mad.2014.03.003. Epub 2014 Mar 24.

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.

Keywords: Cellular senescence; MAPK; PP2C; PPM1B; p38; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation / physiology
  • Cells, Cultured
  • Cellular Senescence / genetics*
  • Fibroblasts
  • Gene Expression Regulation
  • Humans
  • Models, Biological
  • NF-kappa B / metabolism
  • Phosphoprotein Phosphatases / genetics*
  • Protein Phosphatase 2C
  • Transcription Factors
  • Tumor Suppressor Protein p53 / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • NF-kappa B
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • p38 Mitogen-Activated Protein Kinases
  • PPM1A protein, human
  • PPM1B protein, human
  • PPM1G protein, human
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 2C