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YAP enhances the pro‐proliferative transcriptional activity of mutant p53 proteins
Author(s) -
Di Agostino Silvia,
Sorrentino Giovanni,
Ingallina Eleonora,
Valenti Fabio,
Ferraiuolo Maria,
Bicciato Silvio,
Piazza Silvano,
Strano Sabrina,
Del Sal Giannino,
Blandino Giovanni
Publication year - 2016
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540488
Subject(s) - humanities , library science , national park , geography , art , archaeology , computer science
Mutant p53 proteins are present in more than half of human cancers. Yes‐associated protein ( YAP ) is a key transcriptional regulator controlling organ growth, tissue homeostasis, and cancer. Here, we report that these two determinants of human malignancy share common transcriptional signatures. YAP physically interacts with mutant p53 proteins in breast cancer cells and potentiates their pro‐proliferative transcriptional activity. We found YAP as well as mutant p53 and the transcription factor NF‐Y onto the regulatory regions of cyclin A, cyclin B, and CDK 1 genes. Either mutant p53 or YAP depletion down‐regulates cyclin A, cyclin B, and CDK 1 gene expression and markedly slows the growth of diverse breast cancer cell lines. Pharmacologically induced cytoplasmic re‐localization of YAP reduces the expression levels of cyclin A, cyclin B, and CDK 1 genes both in vitro and in vivo . Interestingly, primary breast cancers carrying p53 mutations and displaying high YAP activity exhibit higher expression levels of cyclin A, cyclin B, and CDK 1 genes when compared to wt‐p53 tumors.