IGF-1 activates p21 to inhibit UV-induced cell death

Oncogene. 2003 Mar 20;22(11):1703-11. doi: 10.1038/sj.onc.1206327.

Abstract

The insulin-like growth factor-1 (IGF-1) and its downstream effector Akt have been documented as survival factors in response to a variety of stress signals. In this study, we show that IGF-1 activates p21 protein expression in a p53-dependent manner. Inhibition of PI-3 kinase or ectopic expression of a dominant-negative Akt blocks the effect of IGF-1 on the upregulation of p21 expression. In addition, IGF-1 prevents the UV irradiation-mediated suppression of p21 and MDM2 expression. Furthermore, p21 is important for IGF-1-mediated cell survival upon UV irradiation. Taken together, these data indicate that IGF-1 may activate p21 in executing its survival function upon genotoxic insults.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Apoptosis / radiation effects*
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / physiology*
  • Down-Regulation
  • Humans
  • Insulin-Like Growth Factor I / physiology*
  • Mice
  • Nuclear Proteins*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Serine-Threonine Kinases*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins / physiology
  • Proto-Oncogene Proteins c-akt
  • Proto-Oncogene Proteins c-mdm2
  • Tumor Cells, Cultured
  • Ultraviolet Rays*
  • Up-Regulation

Substances

  • CDKN1A protein, human
  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Insulin-Like Growth Factor I
  • MDM2 protein, human
  • Mdm2 protein, mouse
  • Proto-Oncogene Proteins c-mdm2
  • Phosphatidylinositol 3-Kinases
  • AKT1 protein, human
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt