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The phosphorylation switch that regulates ticking of the circadian clock
How a chemical switch controls the timing of the body’s internal clock
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Abstract
The recent structure of a circadian mutant form of CK1 suggests a mechanism for regulating the internal clock.
- Circadian rhythms are affected by various factors, leading to metabolic, mood, and cancer-related disorders.
- The core clock's regulation involves reversible phosphorylation of PERIOD proteins by casein kinase 1 (CK1) isoforms.
- Phosphorylation at a stabilizing site on PERIOD proteins prevents phosphorylation of a distant degradation site.
- A newly identified internal activation loop in CK1 may play a role in controlling this phosphorylation process.
- Insights from biochemical, genetic, and structural studies have enhanced understanding of the clock's regulation.
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