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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.; Shaw, Peter E.

Authors

Matthew D. Galbraith

Janice Saxton

LI LI li.li@nottingham.ac.uk
Senior Research Fellow

Samuel J. Shelton

Hongmei Zhang

Joaquin M. Espinosa

Peter E. Shaw



Abstract

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.

Citation

Galbraith, M. D., Saxton, J., Li, L., Shelton, S. J., Zhang, H., Espinosa, J. M., & Shaw, P. E. (2013). ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1. Nucleic Acids Research, 41(22), https://doi.org/10.1093/nar/gkt837

Journal Article Type Article
Publication Date Jan 1, 2013
Deposit Date Apr 22, 2014
Publicly Available Date Apr 22, 2014
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 0305-1048
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 41
Issue 22
DOI https://doi.org/10.1093/nar/gkt837
Public URL https://nottingham-repository.worktribe.com/output/1004207
Publisher URL http://nar.oxfordjournals.org/content/41/22/10241.full

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