title: Apoptotic response to growth factor deprivation involves cooperative interactions between c-Fos and p300.
abstract: Two preneoplastic cell lines have been utilized to study changes in the regulation of apoptosis during neoplastic progression [sup+I (stage I) and sup-II (stage II)]. Sup+I cells are prone to undergo apoptosis, while sup-II cells are relatively resistant. We report that induction of apoptosis in sup+I cells is tightly correlated with the formation of c-Fos/p300 complexes, which were not present in the non-apoptotic sup-II cells under the same conditions. When apoptosis was induced in the sup-II cells by over-expression of c-Fos, concomitant c-Fos:p300 complexes were detected. Over-expression of p300 resulted in apoptosis in sup-II cells and also in p53wt human tumor cells, but not in p53mutant human tumor cells. Over-expression of the C-terminal fragment of p300, which contains the c-Fos binding site, enhanced apoptosis, suggesting that the c-Fos:p300 complex is actively involved in apoptosis. We propose that p300 could function as a general mediator of transcription factor-induced apoptosis.
authors.affiliation: Division of Nephrology, Department of Medicine, University of North Carolina Chapel Hill, CD#7155, Chapel Hill, NC 27599, USA. Gloria_Preston@med.unc.edu
authors.forename: G A
authors.initials: GA
authors.lastname: Preston
authors.forename: D
authors.initials: D
authors.lastname: Srinivasan
authors.forename: J C
authors.initials: JC
authors.lastname: Barrett
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D006224:Cricetinae; D005786:Gene Expression Regulation / Q000502:physiology; D016762:Genes, fos / Q000502:physiology*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D009687:Nuclear Proteins / Q000502:physiology*; D011230:Precancerous Conditions / Q000473:pathology; D015534:Trans-Activators / Q000502:physiology*
chemical_list: D006133:Growth Substances; D009687:Nuclear Proteins; D015534:Trans-Activators