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Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation.

Publication ,  Journal Article
Cardinaux, JR; Notis, JC; Zhang, Q; Vo, N; Craig, JC; Fass, DM; Brennan, RG; Goodman, RH
Published in: Mol Cell Biol
March 2000

Phosphorylation of the transcription factor CREB leads to the recruitment of the coactivator, CREB binding protein (CBP). Recent studies have suggested that CBP recruitment is not sufficient for CREB function, however. We have identified a conserved protein-protein interaction motif within the CBP-binding domains of CREB and another transcription factor, SREBP (sterol-responsive element binding protein). In contrast to CREB, SREBP interacts with CBP in the absence of phosphorylation. We have exploited the conservation of this interaction motif to test whether CBP recruitment to CREB is sufficient for transcriptional activation. Substitution of six nonconserved amino acids from SREBP into the activation domain of CREB confers high-affinity, phosphorylation-independent CBP binding. The mutated CREB molecule, CREB(DIEDML), activates transcription in F9 teratocarcinoma and PC12 cells even in the absence of protein kinase A (PKA). Addition of exogenous CBP augments the level of transcription mediated by CREB(DIEDML), and adenovirus 12S E1A blocks transcription, implicating CBP in the activation process. Thus, recruitment of CBP to CREB is sufficient for transcriptional activation. Addition of PKA stimulates transcription induced by CREB(DIEDML) further, suggesting that a phosphorylation event downstream from CBP recruitment augments CREB signaling.

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Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

March 2000

Volume

20

Issue

5

Start / End Page

1546 / 1552

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transcriptional Activation
  • Transcription, Genetic
  • Trans-Activators
  • Signal Transduction
  • Sequence Alignment
  • Nuclear Proteins
  • Mutation
  • Molecular Sequence Data
  • Humans
 

Citation

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Chicago
ICMJE
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Cardinaux, J. R., Notis, J. C., Zhang, Q., Vo, N., Craig, J. C., Fass, D. M., … Goodman, R. H. (2000). Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation. Mol Cell Biol, 20(5), 1546–1552. https://doi.org/10.1128/MCB.20.5.1546-1552.2000
Cardinaux, J. R., J. C. Notis, Q. Zhang, N. Vo, J. C. Craig, D. M. Fass, R. G. Brennan, and R. H. Goodman. “Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation.Mol Cell Biol 20, no. 5 (March 2000): 1546–52. https://doi.org/10.1128/MCB.20.5.1546-1552.2000.
Cardinaux JR, Notis JC, Zhang Q, Vo N, Craig JC, Fass DM, et al. Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation. Mol Cell Biol. 2000 Mar;20(5):1546–52.
Cardinaux, J. R., et al. “Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation.Mol Cell Biol, vol. 20, no. 5, Mar. 2000, pp. 1546–52. Pubmed, doi:10.1128/MCB.20.5.1546-1552.2000.
Cardinaux JR, Notis JC, Zhang Q, Vo N, Craig JC, Fass DM, Brennan RG, Goodman RH. Recruitment of CREB binding protein is sufficient for CREB-mediated gene activation. Mol Cell Biol. 2000 Mar;20(5):1546–1552.

Published In

Mol Cell Biol

DOI

ISSN

0270-7306

Publication Date

March 2000

Volume

20

Issue

5

Start / End Page

1546 / 1552

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Transcriptional Activation
  • Transcription, Genetic
  • Trans-Activators
  • Signal Transduction
  • Sequence Alignment
  • Nuclear Proteins
  • Mutation
  • Molecular Sequence Data
  • Humans