title: The phosphatidyl inositol 3 kinase pathway does not suppress activation of the ARF and BIM genes by deregulated E2F1 activity.
abstract: The transcription factor E2F plays crucial roles in tumor suppression by activating pro-apoptotic genes such as the tumor suppressor ARF. The regulation of the ARF gene is distinct from that of growth-related E2F targets, in that it is specifically activated by deregulated E2F activity, induced by over-expression of E2F or forced inactivation of pRB, but not by physiological E2F activity induced by growth stimulation. The phosphatidyl inositol 3 kinase (PI3K) pathway was reported to suppress expression of some atypical pro-apoptotic genes by over-expressed E2F1. However, the effects of the PI3K pathway on the distinct regulation of typical pro-apoptotic E2F targets have not been elucidated. We examined whether the PI3K pathway suppressed activation of the typical pro-apoptotic E2F targets ARF and BIM. Activation of the PI3K pathway by growth stimulation or introduction of a constitutively active Akt/PKB did not reduce induction of ARF or BIM gene expression or activation of their promoters by over-expressed E2F1. These results suggest that the PI3K pathway does not suppress induction of typical pro-apoptotic genes that are selectively activated by deregulated E2F1.
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Kurayoshi
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Okuno
authors.affiliation: Signalling Laboratory, The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, UK.
authors.forename: Eiko
authors.initials: E
authors.lastname: Ozono
authors.affiliation: Department of Craniofacial Biology, University of Colorado School of Dental Medicine, Anschutz Medical Campus, 12801 E. 17th Avenue, Aurora, CO 80045, USA.
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Iwanaga
authors.affiliation: Department of Obstetrics and Gynecology, University of Colorado School of Medicine, Anschutz Medical Campus, 12800 East 19th Avenue, Aurora, CO 80045, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Bradford
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kugawa
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Araki
authors.affiliation: Department of Biomedical Chemistry, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo, 669-1337, Japan. Electronic address: btm88939@kwansei.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ohtani
mesh_terms: D017209:Apoptosis; D000072224:Bcl-2-Like Protein 11 / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18 / Q000378:metabolism*; D050687:E2F1 Transcription Factor / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000072224:Bcl-2-Like Protein 11; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050687:E2F1 Transcription Factor; D019869:Phosphatidylinositol 3-Kinases; D016160:Retinoblastoma Protein; C000614131:CDKN2A protein, human
keywords: Apoptosis; E2F; Gene regulation; PI3K; RB