MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300.

Journal Article (Journal Article)

CBP/p300 recruitment to enhancer-bound complexes is a key determinant in promoter activation by many transcription factors. We present a novel mechanism of activating such complexes and show that pre-assembled Elk-1-p300 complexes become activated following Elk-1 phosphorylation by changes in Elk-1-p300 interactions rather than recruitment. It is known that Elk-1 binds to promoter in the absence of stimuli. However, it is unclear how activation of Elk-1 by mitogen-acivated protein kinase (MAPK)-mediated phosphorylation leads to targeted gene transactivation. We show that Elk-1 can interact with p300 in vitro and in vivo in the absence of a stimulus through the Elk-1 C-terminus and the p300 N-terminus. Phosphorylation on Ser383 and Ser389 of Elk-1 by MAPK enhances this basal binding but, most importantly, Elk-1 exhibits new interactions with p300. These interaction changes render a strong histone acetyltransferase activity in the Elk-1-associated complex that could play a critical role in chromatin remodeling and gene activation. The pre-assembly mechanism may greatly accelerate transcription activation, which is important in regulation of expression of immediate-early response genes, in particular those involved in stress responses.

Full Text

Duke Authors

Cited Authors

  • Li, Q-J; Yang, S-H; Maeda, Y; Sladek, FM; Sharrocks, AD; Martins-Green, M

Published Date

  • January 15, 2003

Published In

Volume / Issue

  • 22 / 2

Start / End Page

  • 281 - 291

PubMed ID

  • 12514134

Pubmed Central ID

  • PMC140103

International Standard Serial Number (ISSN)

  • 0261-4189

Digital Object Identifier (DOI)

  • 10.1093/emboj/cdg028


  • eng

Conference Location

  • England