[PDF][PDF] Gain of function of mutant p53: the mutant p53/NF-Y protein complex reveals an aberrant transcriptional mechanism of cell cycle regulation
S Di Agostino, S Strano, V Emiliozzi, V Zerbini… - Cancer cell, 2006 - cell.com
S Di Agostino, S Strano, V Emiliozzi, V Zerbini, M Mottolese, A Sacchi, G Blandino…
Cancer cell, 2006•cell.comThis 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 …
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 …
Summary
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.
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