Physical Interaction Between Cyclin-Dependent Kinase 5 (CDK5) and Clock Factors Affects the Circadian Rhythmicity in Peripheral Oscillators

Overview

Journal Clocks Sleep

Publisher MDPI

Date 2022 Mar 24

PMID 35323171

Authors

Jurgen A Ripperger

Rohit Chavan

Urs Albrecht

Andrea Brenna

Affiliations

Soon will be listed here.

Abstract

Circadian rhythms are self-sustained oscillators with a period of 24 h that is based on the output of transcriptional and post-translational feedback loops. Phosphorylation is considered one of the most important post-translational modifications affecting rhythmicity from cyanobacteria to mammals. For example, the lack of cyclin-dependent kinase 5 (CDK5) shortened the period length of the circadian oscillator in the Suprachiasmatic Nuclei (SCN) of mice via the destabilization of the PERIOD 2 (PER2) protein. Here, we show that CDK5 kinase activity and its interaction with clock components, including PER2 and CLOCK, varied over time in mouse embryonic fibroblast cells. Furthermore, the deletion of from cells resulted in a prolonged period and shifted the transcription of clock-controlled genes by about 2 to 4 h with a simple delay of chromatin binding of ARNTL (BMAL1) CLOCK. Taken together, our data indicate that CDK5 is critically involved in regulating the circadian clock in vitro at the molecular level.

Citing Articles

Cyclin-dependent kinase 5 (Cdk5) activity is modulated by light and gates rapid phase shifts of the circadian clock.

Brenna A, Borsa M, Saro G, Ripperger J, Glauser D, Yang Z Elife. 2025; 13.

PMID: 39937180 PMC: 11820109. DOI: 10.7554/eLife.97029.

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