Germ-layer specification and control of cell growth by Ectodermin, a Smad4 ubiquitin ligase

Cell. 2005 Apr 8;121(1):87-99. doi: 10.1016/j.cell.2005.01.033.

Sirio Dupont ¹, Luca Zacchigna, Michelangelo Cordenonsi, Sandra Soligo, Maddalena Adorno, Massimo Rugge, Stefano Piccolo

Affiliations

Affiliation

1 Department of Histology, Microbiology and Medical Biotechnologies, Section of Histology and Embryology, University of Padua, 35121 Padua, Italy.

PMID: 15820681 DOI: 10.1016/j.cell.2005.01.033

Abstract

TGF-beta signaling is essential for development and proliferative homeostasis. During embryogenesis, maternal determinants act in concert with TGF-beta signals to form mesoderm and endoderm. In contrast, ectoderm specification requires the TGF-beta response to be attenuated, although the mechanisms by which this is achieved remain unknown. In a functional screen for ectoderm determinants, we have identified Ectodermin (Ecto). In Xenopus embryos, Ecto is essential for the specification of the ectoderm and acts by restricting the mesoderm-inducing activity of TGF-beta signals to the mesoderm and favoring neural induction. Ecto is a RING-type ubiquitin ligase for SMAD4, a TGF-beta signal transducer. Depletion of Ecto in human cells enforces TGF-beta-induced cytostasis and, moreover, plays a causal role in limiting the antimitogenic effects of SMAD4 in tumor cells. We propose that Ectodermin is a key switch in the control of TGF-beta gene responses during early embryonic development and cell proliferation.

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