Skip to main content

TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein.

Publication ,  Journal Article
Shen, X; Hu, PP; Liberati, NT; Datto, MB; Frederick, JP; Wang, XF
Published in: Mol Biol Cell
December 1998

Smads are intermediate effector proteins that transduce the TGF-beta signal from the plasma membrane to the nucleus, where they participate in transactivation of downstream target genes. We have shown previously that coactivators p300/CREB-binding protein are involved in TGF-beta-mediated transactivation of two Cdk inhibitor genes, p21 and p15. Here we examined the possibility that Smads function to regulate transcription by directly interacting with p300/CREB-binding protein. We show that Smad3 can interact with a C-terminal fragment of p300 in a temporal and phosphorylation-dependent manner. TGF-beta-mediated phosphorylation of Smad3 potentiates the association between Smad3 and p300, likely because of an induced conformational change that removes the autoinhibitory interaction between the N- and C-terminal domains of Smad3. Consistent with a role for p300 in the transcription regulation of multiple genes, overexpression of a Smad3 C-terminal fragment causes a general squelching effect on multiple TGF-beta-responsive reporter constructs. The adenoviral oncoprotein E1A can partially block Smad-dependent transcriptional activation by directly competing for binding to p300. Taken together, these findings define a new role for phosphorylation of Smad3: in addition to facilitating complex formation with Smad4 and promoting nuclear translocation, the phosphorylation-induced conformational change of Smad3 modulates its interaction with coactivators, leading to transcriptional regulation.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Mol Biol Cell

DOI

ISSN

1059-1524

Publication Date

December 1998

Volume

9

Issue

12

Start / End Page

3309 / 3319

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Transcriptional Activation
  • Trans-Activators
  • Smad3 Protein
  • Signal Transduction
  • Protein Conformation
  • Protein Binding
  • Promoter Regions, Genetic
  • Phosphorylation
  • Peptide Fragments
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Shen, X., Hu, P. P., Liberati, N. T., Datto, M. B., Frederick, J. P., & Wang, X. F. (1998). TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein. Mol Biol Cell, 9(12), 3309–3319. https://doi.org/10.1091/mbc.9.12.3309
Shen, X., P. P. Hu, N. T. Liberati, M. B. Datto, J. P. Frederick, and X. F. Wang. “TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein.Mol Biol Cell 9, no. 12 (December 1998): 3309–19. https://doi.org/10.1091/mbc.9.12.3309.
Shen X, Hu PP, Liberati NT, Datto MB, Frederick JP, Wang XF. TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein. Mol Biol Cell. 1998 Dec;9(12):3309–19.
Shen, X., et al. “TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein.Mol Biol Cell, vol. 9, no. 12, Dec. 1998, pp. 3309–19. Pubmed, doi:10.1091/mbc.9.12.3309.
Shen X, Hu PP, Liberati NT, Datto MB, Frederick JP, Wang XF. TGF-beta-induced phosphorylation of Smad3 regulates its interaction with coactivator p300/CREB-binding protein. Mol Biol Cell. 1998 Dec;9(12):3309–3319.

Published In

Mol Biol Cell

DOI

ISSN

1059-1524

Publication Date

December 1998

Volume

9

Issue

12

Start / End Page

3309 / 3319

Location

United States

Related Subject Headings

  • Transforming Growth Factor beta
  • Transcriptional Activation
  • Trans-Activators
  • Smad3 Protein
  • Signal Transduction
  • Protein Conformation
  • Protein Binding
  • Promoter Regions, Genetic
  • Phosphorylation
  • Peptide Fragments