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Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
Published on: February 25, 2016
TFIIH is negatively regulated by cdk8-containing mediator complexes.
S Akoulitchev1, S Chuikov, D Reinberg
1Howard Hughes Medical Institute, Department of Biochemistry, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.
Nature
|September 19, 2000
Summary
Cyclin-dependent kinase 8 (cdk8) regulates transcription by phosphorylating cyclin H, impacting the transcription factor TFIIH. This discovery links the Mediator complex to basal transcription machinery in higher organisms.
Area of Science:
- Molecular Biology
- Gene Regulation
- Biochemistry
Background:
- Cyclin-dependent kinase 8 (cdk8) is implicated in acute lymphoblastic leukaemias and transcription regulation.
- Mammalian cdk8/cyclin C and yeast Srb10/Srb11 are part of the RNA polymerase II holoenzyme, acting as kinases.
- The cdk8/cyclin C complex is found in Mediator-like complexes that repress transcription.
Purpose of the Study:
- To investigate the regulatory mechanism of cdk8/cyclin C on transcription.
- To determine how cdk8/cyclin C interacts with the general transcription initiation factor IIH (TFIIH).
Main Methods:
- Investigated the phosphorylation of mammalian cyclin H by cdk8.
- Assessed the impact of this phosphorylation on TFIIH activity in vitro.
- Examined the in vivo effects of mimicking cdk8 phosphorylation on cyclin H.
Main Results:
- Cdk8 phosphorylates mammalian cyclin H near its unique helical domains.
- This phosphorylation inhibits TFIIH's transcription activation and CTD kinase activity.
- Mimicking cdk8 phosphorylation of cyclin H in vivo caused a dominant-negative effect on cell growth.
Conclusions:
- Cdk8/cyclin C regulates transcription by targeting TFIIH subunits.
- A regulatory pathway involving cdk8 and TFIIH links the Mediator complex and basal transcription machinery.
- This regulatory pathway appears to be specific to higher organisms.
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