AsianScientist (Dec. 1, 2016) – Researchers in Korea have found that the circadian clock drives changes in the circadian rhythms of p53, a tumor suppressor, revealing an important link between the circadian clock and cancer. The findings were published in Proceedings of the National Academy of Sciences.
The circadian clock in our brain controls behavioral and physiological processes within a period of 24 hours, including making us fall asleep at a certain time by triggering the release of the sleep hormone melatonin in our brains at around 9 pm, for example. The clock is also involved in various physiological processes such as cell division, movement, and development. Disruptions caused by the mismatch of the circadian clock and real time due to chronic late night work, shift work, and other similar issues may lead to various diseases such as diabetes, cancer, and heart disease.
Using differential equations, Professor Kim Jae Kyoung from the Department of Mathematical Sciences at KAIST applied a model-driven mathematical approach to learn the mechanism and role of p53. Kim’s mathematical modeling has been validated by experimental studies conducted by a research team at Virginia Polytechnic Institute and State University in the US, which is led by Professor Carla Finkielstein.
In 2014, Finkelstein’s research team succeeded in observing the changes of p53 over a period of 24 hours, but could not understand how the circadian clock controls the 24-hour rhythm of p53. It was difficult to determine p53’s mechanism, since its cell regulation system is far more complex than other cells. To solve the problem, Kim set up a computer simulation using mathematical modeling and ran millions of simulations.
During this process, Kim proved that the biorhythm of p53 and Period2, an important protein in the circadian clock, are closely related. Cells usually consist of a cell nucleus and cytoplasm. While p53 exists in both nucleus and cytoplasm, it becomes more stable and its degradation slows down when it is in the nucleus.
The researchers said that this research will help explain the cause of different results from numerous anticancer drugs, used to normalize the level of p53, when they are administrated at different times; and find the most effective dosing times for the drugs.
The article can be found at: Gotoh et al. (2016) Model-driven Experimental Approach Reveals the Complex Regulatory Distribution of P53 by the Circadian Factor Period 2.
———
Source: Korea Advanced Institute of Science and Technology; Photo: Shutterstock.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.
