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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.

Original publication

DOI

10.1073/pnas.1909393116

Type

Journal article

Journal

Proceedings of the National Academy of Sciences

Publisher

Proceedings of the National Academy of Sciences

Publication Date

27/08/2019

Volume

116

Pages

17470 - 17479