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Fig. 2 | Sleep Science and Practice

Fig. 2

From: A circadian based inflammatory response – implications for respiratory disease and treatment

Fig. 2

Scheme representing the same mammalian cell, e.g. SCN cell, showing the molecular circadian clock sequence of events that under normal entrainment conditions in nature, lasts 24 h. CLOCK and BMAL1 proteins form a heterodimer which activates the transcription of genes encoding other core components of the loop: e.g. Cryptochrome (Cry1 and Cry2), Period (Per1 and Per2), Nr1d1 (REV-ERB-α protein) or Ror-α. CLOCK and BMAL1 also regulate the transcription of the so-called clock controlled genes. Among these genes there are key factors in processes intimately related to immune response. Cry and Per mRNAs are translated into CRY and PER proteins with levels increasing during the night and form a heterodimer. CK1δ and CK1ε phosphorilate CRY and PER proteins allowing their translocation into the nucleus. In the nucleus, the CRY/PER heterodimer represses the BMAL1/CLOCK activity thereby inhibiting their own transcription. CRY and PER proteins are ubiquinated leading to their degradation via the 26S proteosome. CRY and PER levels decrease and with it their repression over BMAL1/CLOCK, allowing for a new cycle to start again and the completion of the 24-h feedback loop. BMAL1/CLOCK also regulate the expression of the nuclear receptors Nr1d1 ( REV-ERB-α protein) and Ror-α ( ROR-α protein) which will, in turn, repress or activate Bmal1 transcription

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