Activation of Smad1-mediated transcription by p300/CBP

作者：Pearson KL; Hunter T; Janknecht R^*

来源：Biochimica et Biophysica Acta-Gene Structure and Expression, 1999, 1489(2-3): 354-364.

DOI：10.1016/S0167-4781(99)00166-9

• CBP
• p300
• phosphorylation
• Smad1
• transcription

Smad 1 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 Smad 1 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 Ga14 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

• 出版日期1999-12-23