Significance TP53 , encoding p53, is the most frequently mutated gene in human cancers. p53 is a transcription factor that suppresses tumors by regulating myriad genes critical for diverse cellular outcomes including growth arrest and death. This study addresses the mechanism by which iASPP, a p53 partner, influences p53 target gene selection. Using next-generation sequencing, we found genes coregulated by iASPP and p53, and characterized their DNA sequence signatures. Our crystal structure of iASPP and p53 reveals that iASPP displaces a loop of p53 that recognizes DNA signatures. iASPP inhibits p53 through a protein surface distinct from other characterized p53 cellular partners but overlapping that targeted by the viral oncoprotein human papillomavirus E6. These findings open prospects for designing p53-targeting anticancer agents.
Journal article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences
27/08/2019
116
17470 - 17479