title: Gain of function of mutant p53: the mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation.
abstract: This article investigates the mechanistic aspects of mutant p53 "gain of function" in response to DNA damage. We show that mutant forms of p53 protein interact with NF-Y. The expression of cyclin A, cyclin B1, cdk1, and cdc25C, as well as the cdk1-associated kinase activities, is upregulated after DNA damage, provoking a mutant p53/NF-Y-dependent increase in DNA synthesis. Mutant p53 binds NF-Y target promoters and, upon DNA damage, recruits p300, leading to histone acetylation. The recruitment of mutant p53 to the CCAAT sites is severely impaired upon abrogation of NF-YA expression. Endogenous NF-Y, mutant p53, and p300 proteins form a triple complex upon DNA damage. We demonstrate that aberrant transcriptional regulation underlies the ability of mutant p53 proteins to act as oncogenic factors.
authors.affiliation: Experimental Oncology Department, Istituto Regina Elena, Via delle Messi D'Oro 156, 00158 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Agostino
authors.forename: Sabrina
authors.initials: S
authors.lastname: Strano
authors.forename: Velia
authors.initials: V
authors.lastname: Emiliozzi
authors.forename: Valentina
authors.initials: V
authors.lastname: Zerbini
authors.forename: Marcella
authors.initials: M
authors.lastname: Mottolese
authors.forename: Ada
authors.initials: A
authors.lastname: Sacchi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Blandino
authors.forename: Giulia
authors.initials: G
authors.lastname: Piaggio
mesh_terms: D001483:Base Sequence; D023081:CCAAT-Binding Factor / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D004249:DNA Damage / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D014158:Transcription, Genetic / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000378:metabolism
chemical_list: D023081:CCAAT-Binding Factor; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors