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Opposing effects of Elk-1 multisite phosphorylation shape its response to ERK activation.

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
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 Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: Science
ISSN: 1095-9203
Language: ENG
Dates:
DateEvent
14 October 2016Published
23 August 2016Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
FC001-190Cancer Research UKhttp://dx.doi.org/10.13039/501100000289
FC001-190Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
FC001-190Wellcome Trusthttp://dx.doi.org/10.13039/100004440
268690European Research Councilhttp://dx.doi.org/10.13039/501100000781
647474European Research Councilhttp://dx.doi.org/10.13039/501100000781
ANR14-ACHN-0015-01Agence Nationale de la Recherchehttp://dx.doi.org/10.13039/501100001665
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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