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Updated: Jan 30, 2026
Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein
Published on: June 30, 2019
Molecular and in vivo Functions of the CDK8 and CDK19 Kinase Modules
Marius Volker Dannappel1,2, Dhanya Sooraj1,2, Jia Jian Loh1,3
1Hudson Institute of Medical Research, Clayton, VIC, Australia.
Abstract:
CDK8 and its paralog, CDK19, collectively termed 'Mediator Kinase,' are cyclin-dependent kinases that have been implicated as key rheostats in cellular homeostasis and developmental programming. CDK8 and CDK19 are incorporated, in a mutually exclusive manner, as part of a 4-protein complex called the Mediator kinase module. This module reversibly associates with the Mediator, a 26 subunit protein complex that regulates RNA Polymerase II mediated gene expression. As part of this complex, the Mediator kinases have been implicated in diverse process such as developmental signaling, metabolic homeostasis and in innate immunity. In recent years, dysregulation of Mediator kinase module proteins, including CDK8/19, has been implicated in the development of different human diseases, and in particular cancer. This has led to intense efforts to understand how CDK8/19 regulate diverse biological outputs and develop Mediator kinase inhibitors that can be exploited therapeutically. Herein, we review both context and function of the Mediator kinases at a molecular, cellular and animal level. In so doing, we illuminate emerging concepts underpinning Mediator kinase biology and highlight certain aspects that remain unsolved.
Insights
Mediator kinases, CDK8 and CDK19, regulate gene expression and cellular processes. Their dysregulation is linked to diseases like cancer, driving research into therapeutic inhibitors.
Area of Science:
- Molecular Biology
- Cellular Biology
- Genetics
Background:
- Cyclin-dependent kinases CDK8 and CDK19, known as Mediator Kinases, are crucial regulators of cellular homeostasis and development.
- They form a distinct module within the larger Mediator complex, influencing RNA Polymerase II transcription.
- Dysregulation of these kinases is increasingly linked to human diseases, particularly cancer.
Purpose of the Study:
- To review the molecular, cellular, and animal-level context and function of Mediator Kinases (CDK8/19).
- To illuminate emerging concepts in Mediator Kinase biology.
- To highlight unsolved aspects of Mediator Kinase function and regulation.
Main Methods:
- Literature review of molecular, cellular, and animal studies.
- Analysis of the role of Mediator Kinases in gene expression regulation.
- Examination of the link between Mediator Kinase dysregulation and disease.
Main Results:
- Mediator Kinases (CDK8/19) play key roles in developmental signaling, metabolic homeostasis, and innate immunity.
- Their involvement in diverse biological outputs is multifaceted.
- Intense research is focused on understanding their function and developing therapeutic inhibitors.
Conclusions:
- Mediator Kinases are critical regulators with significant implications in human health and disease.
- Further research is needed to fully elucidate their complex biology and therapeutic potential.
- Understanding Mediator Kinase function is key for developing novel cancer therapies.
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