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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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Autores principales: Fant, Charli B., Taatjes, Dylan J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2018
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.
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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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