Nijmegen breakage syndrome fibroblasts expressing the C-terminal truncated NBN(p70) protein undergo p38/MK2-dependent premature senescence

Biogerontology. 2015 Feb;16(1):43-51. doi: 10.1007/s10522-014-9530-3. Epub 2014 Sep 12.


Fibroblasts from the progeroid Nijmegen breakage syndrome that express a truncated version of the nibrin protein (NBN(p70)) undergo premature senescence and have an enlarged morphology with high levels of senescence-associated β-galactosidase, although they do not have F-actin stress fibres. Growth of these fibroblasts in the continuous presence of p38 inhibitors resulted in a large increase in replicative capacity and changed the cellular morphology so that the cells resembled young normal fibroblasts. A similar effect was seen using an inhibitor of the p38 downstream effector kinase MK2. These data suggest that NBN(p70) expressing cells undergo a degree of stress-induced replicative senescence via p38/MK2 activation, potentially due to increased telomere dysfunction, that may play a role in the progeroid features seen in this syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / metabolism*
  • Cell Proliferation / physiology
  • Cells, Cultured
  • Cellular Senescence / physiology*
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / metabolism
  • Fibroblasts / pathology*
  • Humans
  • Imidazoles / pharmacology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Nijmegen Breakage Syndrome / metabolism
  • Nijmegen Breakage Syndrome / pathology*
  • Nuclear Proteins / metabolism*
  • Phenotype
  • Protein Serine-Threonine Kinases / metabolism*
  • Pyridines / pharmacology
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Telomere / physiology
  • p38 Mitogen-Activated Protein Kinases / metabolism*


  • Cell Cycle Proteins
  • Enzyme Inhibitors
  • Imidazoles
  • Intracellular Signaling Peptides and Proteins
  • NBN protein, human
  • Nuclear Proteins
  • Pyridines
  • MAP-kinase-activated kinase 2
  • Protein Serine-Threonine Kinases
  • p38 Mitogen-Activated Protein Kinases
  • SB 203580