On phosphorylation and circadian rhythm.

摘要

Circadian rhythm has been well observed from simple unicellular to complex multicellular organisms. Years of studying have identified several genes that are involved in regulation of circadian behavior; nevertheless, the detail mechanisms of how the genetic components influence behavior have not been thoroughly understood. Contemporary notion suggested that there are two components at the molecular level, a set of core clock genes, and a set of output genes. CLK and CYC, transcription factors, and PER and TIM, repressors of CLK and CYC, constitute the core clock machineries, which regulate both the circadian gene expression of both the core clock and output genes.; One of the mechanisms by which molecular clock regulates the period of behavior rhythm seems to involve the speed of PERIOD phosphorylation, since the association of the change in the phosphorylation rate and the period was well documented. PER functions as a repressor, and phosphorylation of PER is likely to contribute to its function, thus, the behavior. Role of phosphorylation has been shown to implicate in its cellular localization, and stability. I have further investigated the role of phosphorylation for its suppression activity, and demonstrated that this modification is critical for its full repression activity. Furthermore, I have identified a possible PER-interacting protein that might play a role in stabilizing and potentiating suppression activity of PER.; Apart from having 24 hours period, circadian system is also capable of adjusting to changes in environment, an entrainment, in which light has been shown to be one of the entrainment factors. CRY and TIM were shown to be involved in light mediating circadian response, although the molecular details were less understood. I showed here an involvement of protein kinase A in the circadian photoreception, and molecularly in TIM degradation.