Ubiquitin-dependent degradation of TGF-beta-activated smad2

Nat Cell Biol. 1999 Dec;1(8):472-8. doi: 10.1038/70258.

Abstract

SMAD proteins are phosphorylated by transforming growth factor-beta (TGF-beta) receptors and translocate to the nucleus, where they control transcription. Here we investigate the fate of activated Smad2. We show that receptor-mediated activation leads to multi-ubiquitination and subsequent degradation of Smad2 by the proteasome. Ubiquitination of Smad2 is a consequence of its accumulation in the nucleus. If degradation is averted, the phosphorylated Smad2 remains in the nucleus in an active state. By targeting Smad2 for destruction, TGF-beta ensures the irreversible termination of its own signalling function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cell Nucleus / drug effects
  • Cell Nucleus / enzymology
  • Cell Nucleus / metabolism
  • Cysteine Endopeptidases / metabolism
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Fluorescent Antibody Technique
  • Half-Life
  • Humans
  • Models, Biological
  • Multienzyme Complexes / antagonists & inhibitors
  • Multienzyme Complexes / metabolism
  • Phosphorylation / drug effects
  • Proteasome Endopeptidase Complex
  • Protein Processing, Post-Translational / drug effects*
  • Signal Transduction / drug effects
  • Smad2 Protein
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Transfection
  • Transforming Growth Factor beta / pharmacology*
  • Ubiquitins / metabolism*

Substances

  • DNA-Binding Proteins
  • Multienzyme Complexes
  • SMAD2 protein, human
  • Smad2 Protein
  • Trans-Activators
  • Transforming Growth Factor beta
  • Ubiquitins
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex