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Science 315 (5813): 840-843

Copyright © 2007 by the American Association for the Advancement of Science

Integration of TGF-ß and Ras/MAPK Signaling Through p53 Phosphorylation

Michelangelo Cordenonsi, Marco Montagner, Maddalena Adorno, Luca Zacchigna, Graziano Martello, Anant Mamidi, Sandra Soligo, Sirio Dupont, Stefano Piccolo*

Abstract: During development and tissue homeostasis, cells must integrate different signals. We investigated how cell behavior is controlled by the combined activity of transforming growth factor–ß (TGF-ß) and receptor tyrosine kinase (RTK) signaling, whose integration mechanism is unknown. We find that RTK/Ras/MAPK (mitogen-activated protein kinase) activity induces p53 N-terminal phosphorylation, enabling the interaction of p53 with the TGF-ß–activated Smads. This mechanism confines mesoderm specification in Xenopus embryos and promotes TGF-ß cytostasis in human cells. These data indicate a mechanism to allow extracellular cues to specify the TGF-ß gene-expression program.

Department of Medical Biotechnologies, Section of Histology and Embryology, University of Padua, Padua, Italy.

* To whom correspondence should be addressed. E-mail: piccolo{at}

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