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Regulatory functions of the Mediator kinases CDK8 and CDK19
The Mediator-associated kinases CDK8 and CDK19 function in the context of three additional proteins: CCNC and MED12, which activate CDK8/CDK19 kinase function, and MED13, which enables their association with the Mediator complex. The Mediator kinases affect RNA polymerase II (pol II) transcription i...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Taylor & Francis
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602567/ https://www.ncbi.nlm.nih.gov/pubmed/30585107 http://dx.doi.org/10.1080/21541264.2018.1556915 |
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author | Fant, Charli B. Taatjes, Dylan J. |
author_facet | Fant, Charli B. Taatjes, Dylan J. |
author_sort | Fant, Charli B. |
collection | PubMed |
description | The Mediator-associated kinases CDK8 and CDK19 function in the context of three additional proteins: CCNC and MED12, which activate CDK8/CDK19 kinase function, and MED13, which enables their association with the Mediator complex. The Mediator kinases affect RNA polymerase II (pol II) transcription indirectly, through phosphorylation of transcription factors and by controlling Mediator structure and function. In this review, we discuss cellular roles of the Mediator kinases and mechanisms that enable their biological functions. We focus on sequence-specific, DNA-binding transcription factors and other Mediator kinase substrates, and how CDK8 or CDK19 may enable metabolic and transcriptional reprogramming through enhancers and chromatin looping. We also summarize Mediator kinase inhibitors and their therapeutic potential. Throughout, we note conserved and divergent functions between yeast and mammalian CDK8, and highlight many aspects of kinase module function that remain enigmatic, ranging from potential roles in pol II promoter-proximal pausing to liquid-liquid phase separation. |
format | Online Article Text |
id | pubmed-6602567 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-66025672019-07-08 Regulatory functions of the Mediator kinases CDK8 and CDK19 Fant, Charli B. Taatjes, Dylan J. Transcription Review The Mediator-associated kinases CDK8 and CDK19 function in the context of three additional proteins: CCNC and MED12, which activate CDK8/CDK19 kinase function, and MED13, which enables their association with the Mediator complex. The Mediator kinases affect RNA polymerase II (pol II) transcription indirectly, through phosphorylation of transcription factors and by controlling Mediator structure and function. In this review, we discuss cellular roles of the Mediator kinases and mechanisms that enable their biological functions. We focus on sequence-specific, DNA-binding transcription factors and other Mediator kinase substrates, and how CDK8 or CDK19 may enable metabolic and transcriptional reprogramming through enhancers and chromatin looping. We also summarize Mediator kinase inhibitors and their therapeutic potential. Throughout, we note conserved and divergent functions between yeast and mammalian CDK8, and highlight many aspects of kinase module function that remain enigmatic, ranging from potential roles in pol II promoter-proximal pausing to liquid-liquid phase separation. Taylor & Francis 2018-12-26 /pmc/articles/PMC6602567/ /pubmed/30585107 http://dx.doi.org/10.1080/21541264.2018.1556915 Text en © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way. |
spellingShingle | Review Fant, Charli B. Taatjes, Dylan J. Regulatory functions of the Mediator kinases CDK8 and CDK19 |
title | Regulatory functions of the Mediator kinases CDK8 and CDK19 |
title_full | Regulatory functions of the Mediator kinases CDK8 and CDK19 |
title_fullStr | Regulatory functions of the Mediator kinases CDK8 and CDK19 |
title_full_unstemmed | Regulatory functions of the Mediator kinases CDK8 and CDK19 |
title_short | Regulatory functions of the Mediator kinases CDK8 and CDK19 |
title_sort | regulatory functions of the mediator kinases cdk8 and cdk19 |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6602567/ https://www.ncbi.nlm.nih.gov/pubmed/30585107 http://dx.doi.org/10.1080/21541264.2018.1556915 |
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