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TGF-beta induces assembly of a Smad2-Smurf2 ubiquitin ligase complex that targets SnoN for degradation.

The receptor-regulated Smad proteins are essential intracellular mediators of signal transduction by the transforming growth factor-beta (TGF-beta) superfamily of growth factors and are also important as regulators of gene transcription. Here we describe a new role for TGF-beta-regulated Smad2 and Smad3 as components of a ubiquitin ligase complex. We show that in the presence of TGF-beta signalling, Smad2 interacts through its proline-rich PPXY motif with the tryptophan-rich WW domains of Smurf2, a recently identified E3 ubiquitin ligases. TGF-beta also induces the association of Smurf2 with the transcriptional co-repressor SnoN and we show that Smad2 can function to mediate this interaction. This allows Smurf2 HECT domain to target SnoN for ubiquitin-mediated degradation by the proteasome. Thus, stimulation by TGF-beta can induce the assembly of a Smad2-Smurf2 ubiquitin ligase complex that functions to target substrates for degradation.

Pubmed ID: 11389444

Authors

  • Bonni S
  • Wang HR
  • Causing CG
  • Kavsak P
  • Stroschein SL
  • Luo K
  • Wrana JL

Journal

Nature cell biology

Publication Data

June 4, 2001

Associated Grants

None

Mesh Terms

  • Amino Acid Motifs
  • Animals
  • Cells, Cultured
  • DNA-Binding Proteins
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Ligases
  • Mink
  • Phosphorylation
  • Proto-Oncogene Proteins
  • Smad2 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • Ubiquitin-Protein Ligases
  • Ubiquitins