Transcriptional integration of mitogenic and mechanical signals by Myc and YAP

• Published in: Genes & development Vol. 31; no. 20; pp. 2017 - 2022
• Main Authors: Croci, Ottavio, De Fazio, Serena, Biagioni, Francesca, Donato, Elisa, Caganova, Marieta, Curti, Laura, Doni, Mirko, Sberna, Silvia, Aldeghi, Deborah, Biancotto, Chiara, Verrecchia, Alessandro, Olivero, Daniela, Amati, Bruno, Campaner, Stefano
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 15.10.2017
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Adaptor Proteins, Signal Transducing - metabolism; Animals; Cell Cycle - genetics; Cell Cycle Proteins; Cell Proliferation - genetics; Cells, Cultured; Intercellular Signaling Peptides and Proteins - physiology; Mechanotransduction, Cellular; Mice; Mice, Transgenic; Phosphoproteins - genetics; Phosphoproteins - metabolism; Proto-Oncogene Proteins c-myc - metabolism; Research Communication; Signal Transduction; Transcription Factors - metabolism; Transcriptional Activation; YAP; Hippo signaling; TEAD; transcription; Myc
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.301184.117

Mammalian cells must integrate environmental cues to determine coherent physiological responses. The transcription factors Myc and YAP-TEAD act downstream from mitogenic signals, with the latter responding also to mechanical cues. Here, we show that these factors coordinately regulate genes required for cell proliferation. Activation of Myc led to extensive association with its genomic targets, most of which were prebound by TEAD. At these loci, recruitment of YAP was Myc-dependent and led to full transcriptional activation. This cooperation was critical for cell cycle entry, organ growth, and tumorigenesis. Thus, Myc and YAP-TEAD integrate mitogenic and mechanical cues at the transcriptional level to provide multifactorial control of cell proliferation.