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Arkadia induces degradation of SnoN and c-Ski to enhance transforming growth factor-beta signaling.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2007 Jul 13; Vol. 282 (28), pp. 20492-501. Date of Electronic Publication: 2007 May 16. - Publication Year :
- 2007
-
Abstract
- Transforming growth factor-beta (TGF-beta) signaling is controlled by a variety of regulators that target either signaling receptors or activated Smad complexes. Among the negative regulators, Smad7 antagonizes TGF-beta signaling mainly through targeting the signaling receptors, whereas SnoN and c-Ski repress signaling at the transcriptional level through inactivation of Smad complexes. We previously found that Arkadia is a positive regulator of TGF-beta signaling that induces ubiquitin-dependent degradation of Smad7 through its C-terminal RING domain. We report here that Arkadia induces degradation of SnoN and c-Ski in addition to Smad7. Arkadia interacts with SnoN and c-Ski in their free forms as well as in the forms bound to Smad proteins, and constitutively down-regulates levels of their expression. Arkadia thus appears to effectively enhance TGF-beta signaling through simultaneous down-regulation of two distinct types of negative regulators, Smad7 and SnoN/c-Ski, and may play an important role in determining the intensity of TGF-beta family signaling in target cells.
- Subjects :
- Animals
COS Cells
Chlorocebus aethiops
DNA-Binding Proteins genetics
Down-Regulation drug effects
Down-Regulation physiology
HeLa Cells
Humans
Intracellular Signaling Peptides and Proteins genetics
Mice
Protein Binding drug effects
Protein Binding physiology
Proto-Oncogene Proteins genetics
Signal Transduction drug effects
Smad7 Protein genetics
Smad7 Protein metabolism
Transcription, Genetic drug effects
Transcription, Genetic physiology
Transforming Growth Factor beta pharmacology
Ubiquitin genetics
Ubiquitin-Protein Ligases
DNA-Binding Proteins metabolism
Intracellular Signaling Peptides and Proteins metabolism
Proto-Oncogene Proteins metabolism
Signal Transduction physiology
Transforming Growth Factor beta metabolism
Ubiquitin metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0021-9258
- Volume :
- 282
- Issue :
- 28
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 17510063
- Full Text :
- https://doi.org/10.1074/jbc.M701294200