Germ-layer specification and control of cell growth by Ectodermin, a Smad4 ubiquitin ligase.
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 RIS Download
Animals | Base Sequence | Blastula | Bone Morphogenetic Protein Receptors | Cell Differentiation | Cell Nucleus | Cell Proliferation | Cells, Cultured | Colon | Colonic Neoplasms | DNA-Binding Proteins | Gene Library | Germ Layers | Humans | Molecular Sequence Data | Receptors, Growth Factor | Signal Transduction | Smad4 Protein | Trans-Activators | Transforming Growth Factor beta | Tripartite Motif Proteins | Ubiquitin-Protein Ligases | Xenopus | Xenopus Proteins