title: YAP enhances the pro-proliferative transcriptional activity of mutant p53 proteins.
abstract: 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 CDK1 genes. Either mutant p53 or YAP depletion down-regulates cyclin A, cyclin B, and CDK1 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 CDK1 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 CDK1 genes when compared to wt-p53 tumors.
authors.affiliation: Translational Oncogenomic Unit, Molecular Medicine Area Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Agostino
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste, Italy Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Sorrentino
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste, Italy Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Ingallina
authors.affiliation: Translational Oncogenomic Unit, Molecular Medicine Area Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Valenti
authors.affiliation: Translational Oncogenomic Unit, Molecular Medicine Area Regina Elena National Cancer Institute, Rome, Italy Molecular Chemoprevention Group, Molecular Medicine Area Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Ferraiuolo
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Piazza
authors.affiliation: Molecular Chemoprevention Group, Molecular Medicine Area Regina Elena National Cancer Institute, Rome, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Strano
authors.affiliation: Laboratorio Nazionale CIB (LNCIB), Area Science Park, Trieste, Italy Dipartimento di Scienze della Vita, Università degli Studi di Trieste, Trieste, Italy blandino@ifo.it delsal@lncib.it.
authors.forename: Giannino
authors.initials: G
authors.lastname: Del Sal
authors.affiliation: Translational Oncogenomic Unit, Molecular Medicine Area Regina Elena National Cancer Institute, Rome, Italy blandino@ifo.it delsal@lncib.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Blandino
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D016203:CDC2 Protein Kinase; D049109:Cell Proliferation; D019925:Cyclin A / Q000235:genetics / Q000378:metabolism; D019926:Cyclin B / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D045325:HCT116 Cells; D006801:Humans; D061986:MCF-7 Cells; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019925:Cyclin A; D019926:Cyclin B; D010750:Phosphoproteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases
keywords: gene expression; metabolism; mutant p53 and YAP; proliferation; statin