ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1
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 histo...
| Main Authors: | , , , , , , |
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| Format: | Article |
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Oxford University Press
2013
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| Online Access: | https://eprints.nottingham.ac.uk/2429/ |
| _version_ | 1848790783346343936 |
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| author | Galbraith, Matthew D. Saxton, Janice Li, Li Shelton, Samuel J. Zhang, Hongmei Espinosa, Joaquin M. Shaw, Peter E. |
| author_facet | Galbraith, Matthew D. Saxton, Janice Li, Li Shelton, Samuel J. Zhang, Hongmei Espinosa, Joaquin M. Shaw, Peter E. |
| author_sort | Galbraith, Matthew D. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T18:18:06Z |
| format | Article |
| id | nottingham-2429 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T18:18:06Z |
| publishDate | 2013 |
| publisher | Oxford University Press |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-24292020-05-04T20:20:13Z https://eprints.nottingham.ac.uk/2429/ 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. 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. Oxford University Press 2013 Article PeerReviewed 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 http://nar.oxfordjournals.org/content/41/22/10241.full doi:10.1093/nar/gkt837 doi:10.1093/nar/gkt837 |
| spellingShingle | Galbraith, Matthew D. Saxton, Janice Li, Li Shelton, Samuel J. Zhang, Hongmei Espinosa, Joaquin M. Shaw, Peter E. ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1 |
| title | ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1 |
| title_full | ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1 |
| title_fullStr | ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1 |
| title_full_unstemmed | ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1 |
| title_short | ERK phosphorylation of MED14 in promoter complexes during mitogen-induced gene activation by Elk-1 |
| title_sort | erk phosphorylation of med14 in promoter complexes during mitogen-induced gene activation by elk-1 |
| url | https://eprints.nottingham.ac.uk/2429/ https://eprints.nottingham.ac.uk/2429/ https://eprints.nottingham.ac.uk/2429/ |