Circadian clock, cancer and lipid metabolism

Genetic analysis has revealed that mammalian circadian oscillator is driven by a cell autonomous transcription/translation-based negative feedback loop, wherein positive elements (CLOCK and BMAL1) induce the expression of negative regulators (Periods, CRY1 and CRY2) that inhibit the transactivation of positive regulators. Recent research reveals that this clock feedback loop affects many aspects of our physiology, such as cell cycle and lipid metabolism. In this review, I summarize the molecular links between the circadian clock mechanism and the cell cycle, and between the clock and lipid metabolism. Recent studies of clock mutants also suggest that clock molecules play a role as stress sensors. Lastly, we propose the importance of sterol for entraining peripheral clocks.