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Cell. April 8, 2005; 121 (1): 87-99.

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

Dupont S , Zacchigna L , Cordenonsi M , Soligo S , Adorno M , Rugge M , Piccolo S .

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.

PubMed ID: 15820681
Article link: Cell.
Grant support: GGP04030 Telethon

Genes referenced: actl6a bmpr1a cer1 chrd.1 eomes fgfr1 isyna1 mixer mixl1 myc myod1 ncam1 psmd6 smad1 smad2 smad4.1 smad4.2 sox2 t tgfb1 tgfbr1 trim24 trim28 trim33 vegt ventx1.2 ventx2.2 wnt8a
Morpholinos referenced: trim33 MO1

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