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Circadian Rhythms and Gene Regulation02:19

Circadian Rhythms and Gene Regulation

The biological clock is involved in many aspects of regulating complex physiology in all animals. It was in 1935 when German zoologists, Hans Kalmus and Erwin Bünning, discovered the existence of circadian rhythm in Drosophila melanogaster. However, the internal molecular mechanisms behind the circadian clock remained a mystery until 1984, when Jeffrey C. Hall, Michael Rosbash, and Michael W. Young discovered the expression of the Per gene oscillating over a 24-hour cycle. In subsequent years,...
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In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells
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CK2alpha phosphorylates BMAL1 to regulate the mammalian clock.

Teruya Tamaru1, Jun Hirayama, Yasushi Isojima

  • 1Department of Physiology, Toho University School of Medicine, Tokyo, Japan.

Nature Structural & Molecular Biology
|March 31, 2009
PubMed
Summary

Casein kinase (CK)-2alpha phosphorylates the core circadian regulator BMAL1, impacting its nuclear accumulation and clock function. This phosphorylation rhythm reveals CK2 as a key regulator of the mammalian circadian system.

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Area of Science:

  • Chronobiology
  • Molecular Biology
  • Biochemistry

Background:

  • Circadian rhythms are fundamental to physiology, controlled by clock proteins.
  • The regulation of clock protein function is complex and involves multiple mechanisms.

Purpose of the Study:

  • To investigate the role of Casein kinase (CK)-2alpha in regulating the core circadian rhythm.
  • To determine if CK2alpha directly phosphorylates BMAL1 and affects its function.

Main Methods:

  • Gene silencing of CK2alpha.
  • Mutation of the Ser90 phosphorylation site in BMAL1.
  • Analysis of nuclear BMAL1 accumulation and circadian clock function.

Main Results:

  • CK2alpha was demonstrated to phosphorylate the core circadian regulator BMAL1.
  • Gene silencing of CK2alpha or mutating BMAL1 at Ser90 impaired nuclear BMAL1 accumulation.
  • Disruption of clock function was observed following CK2alpha manipulation or BMAL1 mutation.
  • Phosphorylation of BMAL1 at Ser90 exhibits a rhythmic pattern.

Conclusions:

  • CK2alpha is an essential regulator of the mammalian circadian system.
  • Phosphorylation of BMAL1 by CK2alpha at Ser90 is critical for proper clock function and nuclear accumulation.