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Structural basis for the versatile interactions of Smad7 with regulator WW domains in TGF-β Pathways.

Aragón E, Goerner N, Xi Q, Gomes T, Gao S, Massagué J, Macias MJ
Structure 20 1726-36 (2012)
Related entries: 2ltv, 2ltw, 2lty, 2ltz

Cited: 63 times
EuropePMC logo PMID: 22921829

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.

Reviews - 2ltx mentioned but not cited (2)

  1. Structural determinants of Smad function in TGF-β signaling. Macias MJ, Martin-Malpartida P, Massagué J. Trends Biochem. Sci. 40 296-308 (2015)
  2. Exploring the Roles of HERC2 and the NEDD4L HECT E3 Ubiquitin Ligase Subfamily in p53 Signaling and the DNA Damage Response. Mathieu NA, Levin RH, Spratt DE. Front Oncol 11 659049 (2021)

Articles - 2ltx mentioned but not cited (1)

  1. Structural basis for the versatile interactions of Smad7 with regulator WW domains in TGF-β Pathways. Aragón E, Goerner N, Xi Q, Gomes T, Gao S, Massagué J, Macias MJ. Structure 20 1726-1736 (2012)


Reviews citing this publication (15)

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