title: IGF-1 activates p21 to inhibit UV-induced cell death.
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.
authors.affiliation: Department of Biochemistry, Boston University School of Medicine, Boston, MA 20118, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Murray
authors.forename: Hongwu
authors.initials: H
authors.lastname: Zheng
authors.forename: Ling
authors.initials: L
authors.lastname: Gu
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Jim Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt; D051736:Proto-Oncogene Proteins c-mdm2; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays; D015854:Up-Regulation
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D007334:Insulin-Like Growth Factor I; D009687:Nuclear Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D051736:Proto-Oncogene Proteins c-mdm2; C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; C497206:MDM2 protein, human; C497207:Mdm2 protein, mouse; C494918:AKT1 protein, human