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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Cardinaux, JR; Notis, JC; Zhang, Q; Vo, N; Craig, JC; Fass, DM; Brennan, RG; Goodman, RH

Published Date

  • March 2000

Published In

Volume / Issue

  • 20 / 5

Start / End Page

  • 1546 - 1552

PubMed ID

  • 10669732

Pubmed Central ID

  • PMC85336

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/MCB.20.5.1546-1552.2000


  • eng

Conference Location

  • United States