The anaphase-promoting complex mediates TGF-beta signaling by targeting SnoN for destruction

Mol Cell. 2001 Nov;8(5):1027-39. doi: 10.1016/s1097-2765(01)00382-3.

Abstract

Degradation of SnoN is thought to play an important role in the transactivation of TGF-beta responsive genes. We demonstrate that the anaphase-promoting complex (APC) is a ubiquitin ligase required for the destruction of SnoN and that the APC pathway is regulated by TGF-beta. The destruction box of SnoN is required for its degradation in response to TGF-beta signaling. Furthermore, the APC activator CDH1 and Smad3 synergistically regulate SnoN degradation. Under these circumstances, CDH1 forms a quaternary complex with SnoN, Smad3, and APC. These results suggest that APC(CDH1) and SnoN play central roles in regulating growth through the TGF-beta signaling system.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Anaphase-Promoting Complex-Cyclosome
  • Animals
  • Antigens, CD
  • Cadherins
  • Cell Cycle / physiology
  • Cell Fractionation
  • Cell Line
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins / metabolism
  • Genes, Reporter
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Ligases / metabolism*
  • Macromolecular Substances
  • Molecular Sequence Data
  • Oocytes / chemistry
  • Oocytes / physiology
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Signal Transduction / physiology*
  • Smad3 Protein
  • Trans-Activators / metabolism
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / metabolism*
  • Ubiquitin-Protein Ligase Complexes*
  • Ubiquitin-Protein Ligases
  • Xenopus laevis

Substances

  • Antigens, CD
  • CDH1 protein, human
  • Cadherins
  • DNA-Binding Proteins
  • Fungal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Macromolecular Substances
  • Proto-Oncogene Proteins
  • Recombinant Fusion Proteins
  • SKIL protein, human
  • SMAD3 protein, human
  • Smad3 Protein
  • Trans-Activators
  • Transcription Factors
  • Transforming Growth Factor beta
  • Ubiquitin-Protein Ligase Complexes
  • Anaphase-Promoting Complex-Cyclosome
  • Ubiquitin-Protein Ligases
  • Ligases