Analysis of an activator:Coactivator complex reveals an essential role for secondary structure in transcriptional activation

David Parker, Ulupi S. Jhala, Ishwar Radhakrishnan, Michael B. Yaffe, Christine Reyes, Andrew I. Shulman, Lewis C. Cantley, Peter E. Wright, Marc Montminy*

*Corresponding author for this work

Research output: Contribution to journalArticle

138 Scopus citations

Abstract

Ser-133 phosphorylation of CREB within the kinase-inducible domain (KID) promotes target gene activation via complex formation with the KIX domain of the coactivator CBP. Concurrent phosphorylation of CREB at Ser-142 inhibits transcriptional induction via an unknown mechanism. Unstructured in the free state, KID folds into a helical structure upon binding to KIX. Using site-directed mutagenesis based on the NMR structure of the KID:KIX complex, we have examined the mechanisms by which Ser-133 and Ser-142 phosphorylation regulate CREB activity. Our results indicate that phospho-Ser-133 stablizes whereas phospho-Ser-142 disrupts secondary structure-mediated interactions between CREB and CBP. Thus, differential phosphorylation of CREB may form the basis by which upstream signals regulate the specificity of target gene activation.

Original languageEnglish (US)
Pages (from-to)353-359
Number of pages7
JournalMolecular cell
Volume2
Issue number3
DOIs
StatePublished - Sep 1998

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Analysis of an activator:Coactivator complex reveals an essential role for secondary structure in transcriptional activation'. Together they form a unique fingerprint.

  • Cite this

    Parker, D., Jhala, U. S., Radhakrishnan, I., Yaffe, M. B., Reyes, C., Shulman, A. I., Cantley, L. C., Wright, P. E., & Montminy, M. (1998). Analysis of an activator:Coactivator complex reveals an essential role for secondary structure in transcriptional activation. Molecular cell, 2(3), 353-359. https://doi.org/10.1016/S1097-2765(00)80279-8