Mylona, A; Theillet, F-X; Foster, C; Cheng, TM; Miralles, F; Bates, PA; Selenko, P; Treisman, R
(2016)
Opposing effects of Elk-1 multisite phosphorylation shape its response to ERK activation.
Science, 354 (6309).
pp. 233-237.
ISSN 1095-9203
https://doi.org/10.1126/science.aad1872
SGUL Authors: Miralles Arenas, Francisco
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Abstract
Multisite phosphorylation regulates many transcription factors, including the serum response factor partner Elk-1. Phosphorylation of the transcriptional activation domain (TAD) of Elk-1 by the protein kinase ERK at multiple sites potentiates recruitment of the Mediator transcriptional coactivator complex and transcriptional activation, but the roles of individual phosphorylation events had remained unclear. Using time-resolved nuclear magnetic resonance spectroscopy, we found that ERK2 phosphorylation proceeds at markedly different rates at eight TAD sites in vitro, which we classified as fast, intermediate, and slow. Mutagenesis experiments showed that phosphorylation of fast and intermediate sites promoted Mediator interaction and transcriptional activation, whereas modification of slow sites counteracted both functions, thereby limiting Elk-1 output. Progressive Elk-1 phosphorylation thus ensures a self-limiting response to ERK activation, which occurs independently of antagonizing phosphatase activity.
Item Type: | Article | |||||||||||||||||||||
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Additional Information: | This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on Vol 354, 14 Oct 2016, DOI: 10.1126/science.aad1872 | |||||||||||||||||||||
Keywords: | General Science & Technology, MD Multidisciplinary | |||||||||||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) > Centre for Biomedical Education (INMEBE) |
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Journal or Publication Title: | Science | |||||||||||||||||||||
ISSN: | 1095-9203 | |||||||||||||||||||||
Language: | ENG | |||||||||||||||||||||
Publisher License: | Publisher's own licence | |||||||||||||||||||||
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PubMed ID: | 27738173 | |||||||||||||||||||||
Go to PubMed abstract | ||||||||||||||||||||||
URI: | https://openaccess.sgul.ac.uk/id/eprint/108246 | |||||||||||||||||||||
Publisher's version: | https://doi.org/10.1126/science.aad1872 |
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