Structural basis for the versatile interactions of Smad7 with regulator WW domains in TGF-β pathways Journal Article
| Authors: | Aragón, E.; Goerner, N.; Xi, Q.; Gomes, T.; Gao, S.; Massague, J.; Macias, M. J. |
| Article Title: | Structural basis for the versatile interactions of Smad7 with regulator WW domains in TGF-β pathways |
| Abstract: | Transforming growth factor (TGF)-β and BMP signaling is mediated by Smads 1-5 (R-Smads and Co-Smads) and inhibited by Smad7, a major hub of regulation of TGF-β and BMP receptors by negative feedback and antagonistic signals. The transcription coactivator YAP and the E3 ubiquitin ligases Smurf1/2 and Nedd4L target R-Smads for activation or degradation, respectively. Pairs of WW domain in these regulators bind PY motifs and adjacent CDK/MAPK and GSK3 phosphorylation sites in R-Smads in a selective and regulated manner. In contrast, here we show that Smad7 binds YAP, Smurf1, Smurf2, and Nedd4L constitutively, the binding involving a PY motif in Smad7 and no phosphorylation. We also provide a structural basis for how regulators that use WW domain pairs for selective interactions with R-Smads, resort to one single versatile WW domain for binding Smad7 to centralize regulation in the TGF-β and BMP pathways. © 2012 Elsevier Ltd. |
| Journal Title: | Structure |
| Volume: | 20 |
| Issue: | 10 |
| ISSN: | 0969-2126 |
| Publisher: | Cell Press |
| Date Published: | 2012-10-10 |
| Start Page: | 1726 |
| End Page: | 1736 |
| Language: | English |
| DOI: | 10.1016/j.str.2012.07.014 |
| PROVIDER: | scopus |
| PMCID: | PMC3472128 |
| PUBMED: | 22921829 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 1" - "Export Date: 2 November 2012" - "CODEN: STRUE" - "Source: Scopus" |
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