Activation of Smad1-mediated transcription by p300/CBP.
Smad1 is the intracellular effector of bone morphogenetic proteins (BMPs), a growth factor family well known to stimulate bone and cartilage formation. Smad1 becomes phosphorylated by the cognate BMP transmembrane receptor protein kinases, associates with the common mediator Smad4 and translocates to the nucleus where it is involved in regulation of gene transcription. In this report we demonstrate that Smad1 interacts with the paralogous coactivators p300 and CBP both in vitro and in vivo. The N- and C-termini of Smad1 negatively interfere with binding to p300/CBP, and the C-terminal half of Smad1 harbors two interaction domains both binding to the same region near the C-terminus of p300/CBP. We show that Smad1 as well as a Gal4 fusion with the C-terminal half of Smad1 stimulate gene transcription in a cooperative fashion with p300/CBP. Phosphorylation of Smad1 enhances its binding to CBP and thereby further stimulates Smad1-dependent transcription. These results provide a mechanism how phosphorylated Smad1 regulates gene activity by interaction with p300/CBP, and factors associated with these bridging coactivators.
Pearson
K L
KL
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Hunter
T
T
Janknecht
R
R
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D050881:E1A-Associated p300 Protein; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D051381:Rats; D051785:Smad Proteins; D051898:Smad1 Protein; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C497399:SMAD1 protein, human; D051785:Smad Proteins; D051898:Smad1 Protein; C497400:Smad1 protein, rat; D015534:Trans-Activators; D050881:E1A-Associated p300 Protein; C494362:Ep300 protein, rat