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Beschreibung

Cryptochrome-1 (UniProt: P97784) is encoded by the Cry1 gene (Gene ID: 12952) in murine species. Cryptochrome-1 is an evolutionarily conserved member of the flavoprotein superfamily that acts as a transcriptional repressor and forms a core component of the circadian clock. It has a photolyase domain at its N-terminal (aa 3-132). Cryptochrome-1 has three FAD biding sites (aa 252, 289, and 355). However, only a minority of the protein molecules contain bound FAD. Transcription and translation of core clock components (CLOCK, NPAS2, ARNTL/BMAL1, ARNTL2/BMAL2, PER1, PER2, PER3, CRY1 and CRY2) play a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndrome, and aging. Crytopchrome-1 translocates to the nucleus through interaction with other clock proteins such as PER2 or ARNTL/BMAL1. The core clock genes: PER1/2/3 and CRY1/2, which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-ARNTL/BMAL1|ARNTL2/BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. Transcription factors, CLOCK or NPAS2 and ARNTL/BMAL1 or ARNTL2/BMAL2, form the positive limb of the feedback loop and act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes. It has been suggested that cryptochrome may act as a molecular gatekeeper to maintain CLOCK-ARNTL/BMAL1 in a poised and repressed state until the proper time for transcriptional activation. Animals with defective cryptochrome-1 display disruption in their glucose homeostasis with elevated blood glucose in response to acute feeding after an overnight fast and severely impaired glucose clearance in a glucose tolerance test.