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The Balance between Acetylation and Deacetylation Controls Smad7 Stability
- Source :
- Journal of Biological Chemistry. 280:21797-21803
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- Transforming growth factor beta (TGFbeta) regulates multiple cellular processes via activation of Smad signaling pathways. We have recently demonstrated that the inhibitory Smad7 interacts with the acetyl transferase p300 and that p300 acetylates Smad7 on two lysine residues. These lysine residues are critical for Smurf-mediated ubiquitination of Smad7, and acetylation protects Smad7 from TGFbeta-induced degradation. In this study we demonstrate that Smad7 interacts with specific histone deacetylases (HDACs) and that the same HDACs are able to deacetylate Smad7. The interaction with HDACs is dependent on the C-terminal MH2 domain of Smad7. In addition, HDAC1-mediated deacetylation of Smad7 decreases the stability of Smad7 by enhancing its ubiquitination. Thus, our results demonstrate that the degradation of Smad7 is regulated by the balance between acetylation, deacetylation and ubiquitination, indicating that this could be a general mechanism to regulate the stability of cellular proteins.
- Subjects :
- Time Factors
Protein Conformation
Immunoblotting
Lysine
SMAD
Plasma protein binding
Biology
Transfection
Models, Biological
Biochemistry
Histone Deacetylases
Cell Line
Smad7 Protein
Histones
Ubiquitin
Transforming Growth Factor beta
Humans
Immunoprecipitation
Transferase
RNA, Small Interfering
Molecular Biology
Glutathione Transferase
integumentary system
Acetylation
DNA
Cell Biology
Transforming growth factor beta
Recombinant Proteins
Protein Structure, Tertiary
Cell biology
DNA-Binding Proteins
Histone
Trans-Activators
biology.protein
Plasmids
Protein Binding
Signal Transduction
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 280
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....878e550e69faa82f998a918a5b093c0d