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AKT keeps the beat in CLOCK's circadian rhythm
Masayuki Noguchi1, Noriyuki Hirata2, Futoshi Suizu2
1From the Division of Cancer Biology, Institute for Genetic Medicine, Hokkaido University, 060-0815, N15 W7 Kita-Ku, Sapporo, Japan m_noguch@igm.hokudai.ac.jp.
The Journal of Biological Chemistry
|June 10, 2018
Summary
The circadian clock regulates gene expression. AKT kinase phosphorylates the CLOCK transcription factor, controlling its movement and circadian gene regulation in tissues.
Area of Science:
- Chronobiology
- Molecular Biology
- Gene Regulation
Background:
- The circadian clock is crucial for physiological and medical processes.
- Post-translational modifications are known regulators of core clock components.
- The complete regulatory network of the circadian clock remains incompletely understood.
Purpose of the Study:
- To investigate the regulatory mechanisms governing the circadian clock.
- To identify novel post-translational modifications affecting clock components.
- To elucidate the role of AKT kinase in circadian rhythm regulation.
Main Methods:
- Investigated the interaction between AKT kinase and the CLOCK transcription factor.
- Utilized biochemical assays to confirm CLOCK as a direct substrate of AKT.
- Examined the impact of AKT-mediated phosphorylation on CLOCK's subcellular localization.
Main Results:
- Demonstrated that the transcription factor CLOCK is a direct substrate of AKT kinase.
- Showed that AKT-mediated phosphorylation of CLOCK regulates its nuclear-cytosolic translocation.
- Confirmed that this regulation impacts CLOCK's ability to control circadian gene expression in peripheral tissues.
Conclusions:
- AKT kinase directly phosphorylates the CLOCK transcription factor.
- Phosphorylation by AKT is a key mechanism controlling CLOCK localization and function.
- This finding provides new insights into the regulation of circadian rhythms in peripheral tissues.