ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1

Galbraith, Matthew D., Saxton, Janice, Li, Li, Shelton, Samuel J., Zhang, Hongmei, Espinosa, Joaquin M. and Shaw, Peter E. (2013) ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1. Nucleic Acids Research, 41 (22). pp. 10241-10253. ISSN 0305-1048

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The ETS domain transcription factor Elk-1 stimulates expression of immediate early genes (IEGs) in response to mitogens. These events require phosphorylation of Elk-1 by extracellular signal-regulated kinase (ERK) and phosphorylation-dependent interaction of Elk-1 with co-activators, including histone acetyltransferases and the Mediator complex. Elk-1 also recruits ERK to the promoters of its target genes, suggesting that ERK phosphorylates additional substrates in transcription complexes at mitogen-responsive promoters. Here we report that MED14, a core subunit of the Mediator, is a bona fide ERK substrate and identify serine 986 (S986) within a serine-proline rich region of MED14 as the major ERK phosphorylation site. Mitogens induced phosphorylation of MED14 on S986 at IEG promoters; RNAi knockdown of MED14 reduced CDK8 and RNA polymerase II (RNAPII) recruitment, RNAPII C-terminal domain phosphorylation and impaired activation of IEG transcription. A single alanine substitution at S986 reduced activation of an E26 (ETS)-responsive reporter by oncogenic Ras and mitogen-induced, Elk-1-dependent transcription, whereas activities of other transcriptional activators were unaffected. We also demonstrate that Elk-1 can associate with MED14 independently of MED23, which may facilitate phosphorylation of MED14 by ERK to impart a positive and selective impact on mitogen-responsive gene expression.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number:
Depositing User: Davies, Mrs Sarah
Date Deposited: 22 Apr 2014 14:07
Last Modified: 04 May 2020 20:20

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