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
-
AKT1 protein, human
-
Protein Serine-Threonine Kinases
-
Proto-Oncogene Proteins c-akt