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| Subject Categories: Signal Transduction | Chromatin & Transcription |
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| The EMBO Journal
(2003) 22, 281–291, doi:10.1093/emboj/cdg028 |
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| MAP kinase phosphorylation-dependent activation of Elk-1 leads to activation of the co-activator p300 |
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| Qi-Jing Li1, Shen-Hsi Yang2, Yutaka Maeda1, Frances M. Sladek1, Andrew D. Sharrocks2 and Manuela Martins-Green1 |
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1 Department of Cell Biology and Neuroscience, University of California, Riverside, CA 92521, USA 2 School of Biological Sciences, University of Manchester, 2.205 Stopford Building, Oxford Road, Manchester M13 9PT, UK To whom correspondence should be addressed Manuela Martins-Green, mmgreen@ucrac1.ucr.edu Received 2 May 2002; Revised 6 November 2002; Accepted 19 November 2002. |
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| Abstract |
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| 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. |
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| Keywords: chemokine, co-activators, Elk-1, p300, transcription activation |
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