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

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.
Mesh Terms:
Acetyltransferases, Animals, Chick Embryo, DNA-Binding Proteins, Enzyme Inhibitors, Fibroblasts, Histone Acetyltransferases, Mitogen-Activated Protein Kinases, Models, Biological, Nuclear Proteins, Phosphorylation, Promoter Regions, Genetic, Proto-Oncogene Proteins, Recombinant Fusion Proteins, Saccharomyces cerevisiae Proteins, Thrombin, Trans-Activators, Transcription Factors, Transcriptional Activation, ets-Domain Protein Elk-1
EMBO J.
Date: Jan. 15, 2003
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