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Smad3 is acetylated by p300/CBP to regulate its transactivation activity
1Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University, Mizuho, Nagoya, Japan.
Oncogene
|July 25, 2006
Summary
Transforming growth factor-beta (TGF-beta) signaling involves Smad proteins. This study reveals that p300/CBP acetylates Smad3, enhancing its transcriptional activity, a key finding for understanding TGF-beta pathway regulation.
Area of Science:
- Molecular Biology
- Cell Signaling
Background:
- Smad proteins mediate intracellular signaling for transforming growth factor-beta (TGF-beta).
- Activated Smad proteins translocate to the nucleus to regulate gene transcription.
Purpose of the Study:
- To investigate the role of p300/CBP in Smad protein regulation.
- To determine if p300/CBP acetylates Smad proteins and how this affects transcriptional activity.
Main Methods:
- In vivo binding and acetylation assays of Smad2 and Smad3 by p300/CBP.
- TGF-beta stimulation to observe acetylation changes.
- Site-directed mutagenesis of Smad3 at Lys-378.
- Luciferase reporter assays using GAL4-Smad3C constructs.
Main Results:
- p300/CBP binds and acetylates Smad2 and Smad3 in vivo, an event stimulated by TGF-beta.
- Lys-378 in the Smad3 MH2 domain is a major acetylation site.
- Mutation of Lys-378 to Arg reduced Smad3 transcriptional activity.
- p300/CBP potentiated the transcriptional activity of wild-type Smad3 but not the K378R mutant.
Conclusions:
- Acetylation of Smad3 by p300/CBP positively regulates its transcriptional activity.
- This acetylation mechanism is a critical component of TGF-beta signaling pathways.
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