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

Shirin Bonni, Hong Rui Wang, Carrie G. Causing, Peter Kavsak, Shannon L. Stroschein, Kunxin Luo, Jeffrey L. Wrana

Research output: Contribution to journalArticlepeer-review

256 Scopus citations

Abstract

The receptor-regulated Smad proteins are essential intracellular mediators of signal transduction by the transforming growth factor-β (TGF-β) superfamily of growth factors and are also important as regulators of gene transcription. Here we describe a new role for TGF-β-regulated Smad2 and Smad3 as components of a ubiquitin ligase complex. We show that in the presence of TGF-β signalling, Smad2 interacts through its proline-rich PPXY motif with the tryptophan-rich WW domains of Smurf2, a recently identified E3 ubiquitin ligases. TGF-β 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-β can induce the assembly of a Smad2-Smurf2 ubiquitin ligase complex that functions to target substrates for degradation.

Original languageEnglish (US)
Pages (from-to)587-595
Number of pages9
JournalNature Cell Biology
Volume3
Issue number6
DOIs
StatePublished - Jun 26 2001

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