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Cyclin-dependent kinase 5 (CDK5) regulates the circadian clock
Andrea Brenna1, Iwona Olejniczak1, Rohit Chavan1
1Department of Biology, University of Fribourg, Fribourg, Switzerland.
Elife
|November 6, 2019
Summary
Cyclin-dependent kinase 5 (CDK5) regulates the mammalian circadian clock by phosphorylating Period 2 (PER2). This action is crucial for PER2
Area of Science:
- Molecular Biology
- Chronobiology
- Cell Biology
Background:
- Circadian rhythms are essential biological processes regulated by complex feedback loops.
- Nuclear translocation of clock proteins is a key step in generating circadian rhythmicity.
- The specific kinase regulating the nuclear import of Period 2 (PER2) in mammals remained unidentified.
Purpose of the Study:
- To identify the kinase responsible for regulating the nuclear import of the mammalian circadian clock component PER2.
- To elucidate the mechanism by which this kinase influences the circadian clock.
Main Methods:
- Investigated the role of cyclin-dependent kinase 5 (CDK5) in the mammalian circadian clock.
- Performed knock-down experiments of CDK5 in the suprachiasmatic nuclei (SCN) of mice.
- Utilized phosphorylation site analysis (serine 394) and protein interaction studies (PER2-CRY1 complex).
Main Results:
- Knock-down of CDK5 in the SCN shortened the free-running period in mice.
- CDK5 was found to phosphorylate PER2 at serine 394 (S394) in a diurnal manner.
- Phosphorylation of PER2 by CDK5 enhanced its interaction with Cryptochrome 1 (CRY1) and facilitated nuclear entry.
Conclusions:
- CDK5 plays a critical role in regulating the mammalian circadian clock by driving the nuclear entry of PER2.
- CDK5-mediated PER2 phosphorylation is essential for maintaining an adequate circadian period.
- CDK5 may regulate other clock components, suggesting its broader involvement in circadian rhythmicity and potential links to circadian-related diseases.
Keywords:
Cryptochrome 1Period 2S. cerevisiaebiochemistrychemical biologymouseneurosciencenuclear importphosphorylationproteasomeMore Related Videos
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