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Updated: Jan 26, 2026
05:46
Recording and Analysis of Circadian Rhythms in Running-wheel Activity in Rodents
Published on: January 24, 2013
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CDK9 modulates circadian clock by attenuating REV-ERBα activity
Jiali Ou1, Huilin Li1, Peiyuan Qiu2
1CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Nutrition and Health, Shanghai Institute for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
Biochemical and Biophysical Research Communications
|April 22, 2019
Summary
Cyclin-dependent kinase 9 (CDK9) modulates the circadian clock by regulating Bmal1 expression. This discovery offers new insights into circadian clock regulation and related diseases like cancer.
Area of Science:
- Molecular Biology
- Chronobiology
- Cellular Biology
Background:
- The circadian clock and cell cycle are crucial, time-regulated cellular processes.
- These two oscillators are interconnected to regulate biological functions.
Purpose of the Study:
- To investigate the role of Cyclin-dependent kinase 9 (CDK9) in modulating the circadian clock.
- To identify potential therapeutic targets for circadian and cell cycle-related disorders.
Main Methods:
- Screening of CDK inhibitors to identify modulators of circadian clock gene expression (PER2:LUC).
- Utilizing siRNA to confirm CDK9 as the effector of inhibitor LY2857785.
- Investigating the interaction between CDK9 and REV-ERBα.
- Performing in vivo studies by knocking down CDK9 in mice.
Main Results:
- CDK inhibitor LY2857785 was identified to block PER2:LUC expression, with CDK9 confirmed as the primary target.
- CDK9 knockdown or LY2857785 treatment resulted in decreased Bmal1 and increased Rev-Erbα expression.
- CDK9 was found to associate with REV-ERBα, inhibiting its binding to RORE and suppressing Bmal1.
- In vivo CDK9 knockdown in mice altered respiratory exchange ratio, daily activity, and circadian period.
Conclusions:
- CDK9 acts as a novel modulator of the circadian clock.
- CDK9's role in circadian regulation provides a potential basis for understanding and treating diseases involving circadian and cell cycle dysregulation, such as cancer.
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