Scientists from Duke-NUS Medical School and the University of California, Santa Cruz have discovered how to regulate our internal clock by identifying a regulator located at the tail end of Casein Kinase 1 delta (CK1δ), a protein that controls the body’s circadian rhythm. Published in the journal PNAS, their findings could lead to new treatments for disorders related to the body clock. CK1δ regulates circadian rhythms by tagging other proteins involved in the biological clock, fine-tuning the timing of these rhythms. The protein itself can also be tagged, altering its ability to regulate the body’s internal clock.
Previous research identified two versions of CK1δ with small differences that significantly impact the protein’s function. This latest study used advanced techniques to zoom in on the proteins’ tails and found that phosphorylation of specific sites on the tail is crucial for controlling CK1δ’s activity. When these sites are tagged with a phosphate group, CK1δ becomes less active, influencing circadian rhythms less effectively. This discovery sheds light on how small alterations in CK1δ can have a big impact on its overall activity, which is crucial for maintaining balanced activity and regulating circadian rhythms.
The researchers found that the different versions of CK1δ interact differently with their tails, leading to varying levels of self-inhibition. Mutations or removal of certain sites on the tail can result in increased activity of CK1δ, leading to changes in circadian rhythms. This new understanding of CK1δ’s self-regulation could have implications beyond circadian rhythms, influencing processes such as cell division, cancer development, and certain neurodegenerative diseases. By better understanding how CK1δ’s activity is regulated, scientists may uncover new approaches for treating a range of conditions.
The implications of this discovery extend to improving sleep quality, metabolism, and overall health, beyond just curing jet lag. By better understanding how CK1δ is regulated, new treatments could be developed to manage these essential aspects of daily life. The researchers plan to investigate how factors like diet and environmental changes affect the tagging sites on CK1δ, providing insights into how circadian rhythms are influenced by real-world factors and potentially leading to practical solutions for managing disruptions.
Duke-NUS Medical School, a global leader in medical education and biomedical research, is driving breakthroughs in scientific research to benefit communities worldwide. By combining scientific research with translational methods, the school is deepening our understanding of prevalent diseases and developing innovative treatment approaches. This latest discovery on regulating the body’s internal clock through CK1δ could pave the way for new treatments for a range of conditions beyond circadian rhythm disorders, ultimately impacting overall health and well-being.
