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

Nat Cell Biol. 2001 Jun;3(6):587-95. doi: 10.1038/35078562.

S Bonni ¹, H R Wang, C G Causing, P Kavsak, S L Stroschein, K Luo, J L Wrana

Affiliations

Affiliation

1 Program in Molecular Biology and Cancer, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario M5G 1X5, Canada.

PMID: 11389444 DOI: 10.1038/35078562

Abstract

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.

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