The transcriptional coactivator yes-associated protein drives p73 gene-target specificity in response to DNA damage

Sabrina Strano, Olimpia Monti, Natalia Pediconi, Alessia Baccarini, Giulia Fontemaggi, Eleonora Lapi, Fiamma Mantovani, Alexander Damalas, Gennaro Citro, Ada Sacchi, Giannino Del Sal, Massimo Levrero, Giovanni Blandino

Research output: Contribution to journalArticlepeer-review

Abstract

The transcriptional coactivator Yes-associated protein (YAP) has been shown to interact with and to enhance p73-dependent apoptosis in response to DNA damage. Here, we show that YAP requires the promyelocytic leukemia gene (PML) and nuclear body localization to coactivate p73. YAP imparts selectivity to p73 by promoting the activation of a subset of p53 and/or p73 target promoters. Endogenous p73, YAP, and p300 proteins are concomitantly recruited onto the regulatory regions of the apoptotic target gene p53AIP1 only when cells are exposed to apoptotic conditions. Silencing of YAP by specific siRNA impairs p300 recruitment and reduces histone acetylation on the p53AIP1 target gene, resulting in delayed or reduced apoptosis mediated by p73. We also found that YAP contributes to the DNA damage-induced accumulation of p73 and potentiates the p300-mediated acetylation of p73. Altogether, our findings identify YAP as a key determinant of p73 gene targeting in response to DNA damage.

Original languageEnglish
Pages (from-to)447-459
Number of pages13
JournalMolecular Cell
Volume18
Issue number4
DOIs
Publication statusPublished - May 13 2005

ASJC Scopus subject areas

  • Molecular Biology

Fingerprint Dive into the research topics of 'The transcriptional coactivator yes-associated protein drives p73 gene-target specificity in response to DNA damage'. Together they form a unique fingerprint.

Cite this