Журнал канцерогенеза и мутагенеза

Абстрактный

Interlink between Nuclear Receptors, Posttranslational Modifications and the Biological Clock in Health and Diseases

Thomas W Owens, Andrew P Gilmore, Charles H Streuli and Fiona M Foster

The day and night cycle influences the body function in health and disease through the modulation of the biological clock in via the suprachiasmatic nucleus (SCN) which in turn acts as the master clock in aligning the downstream clocks in the peripheral organs. The peripheral clocks can also be entrained independently by different factors such as external nutritional, hormonal and chemical cues that in many cases come from ligand modulation of nuclear receptors and kinase activators. Disruption of the molecular clock is associated with many diseases including cancer, immune diseases and aging. In addition, administration of toxic drugs such as anti-cancer can disturb the clock. These examples lead to changes in the sleep pattern of the patient and consequently can accelerate the manifestation of disease. This review details the function of the molecular clock in health and disease and how nuclear receptors and posttranslational modifications interact with the clock to regulate its function. In addition this review describes how chronotherapy can be applied in the clinical setting to treat cancer patients