PNAS: A Key Switch in Biological Clocks Found

Multipoint phosphorylation of the PERIOD 2 (PER2) protein is a critical step in determining the mammalian clock cycle. Previous studies have suggested that the phosphorylation of PER2 by casein kinase 1 (CK1) requires the initiation of an undiscovered protein kinase. CK1 is an essential circulatory protein that is highly conserved from algae to humans. These phosphorylation processes stabilize the PER2 and delay its degradation to extend the circadian clock cycle.

 

 

To find this essential protein, an international team led by Duke-NUS Medical School researchers conducted an integrated biochemical and biophysical analysis of the process of phosphorylation of mouse PER2, and was surprised to find that CK1δ/ε is the priming kinase they are looking for. In addition, they also found that CK1ε and a recently discovered CK1δ2 splice variant can initiate phosphorylation more efficiently than CK1δ1.

 

Although past studies have shown that the phosphorylation of PER2 by CK1 is very insensitive to the cellular environment, the researchers discovered that the carboxy-terminal tail of CK1 makes the clock cycle sensitive to cellular signals by using a mathematical model of the biorhythm phosphorylation switch.

 

These studies indicate that the carboxyl terminus of CK1 is an important regulator of biological rhythms.

 

 

 

Reference

Rajesh Narasimamurthy et al, CK1δ/ε protein kinase primes the PER2 circadian phosphoswitch, Proceedings of the National Academy of Sciences (2018). DOI: 10.1073/pnas.1721076115