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. Author manuscript; available in PMC: 2017 Nov 7.
Published in final edited form as: N Engl J Med. 2015 Jul 2;373(1):60–72. doi: 10.1056/NEJMra1313341

Figure 4. Molecular Mechanism of the Mammalian Circadian Clock.

Figure 4

The core cycle is shown on the right, with an increase in the amount of period circadian clock proteins 1 through 3 (PER1–3) and cryptochrome proteins 1 and 2 (CRY1–2) throughout the day, which acts to suppress their transcription. The red diamonds represent repressor proteins, and the blue ovals, activator proteins. Both activators and repressors are transcription factors or transcription regulators. The rectangles represent genes that encode the respective proteins. CSNK1E encodes casein kinase 1 epsilon, a kinase that is known to alter the period of the circadian oscillator through the phosphorylation (P) of core clock proteins, as shown. CSNK1E (also called CK1ε) is shown in gray because it is neither a transcriptional activator nor a repressor. BMAL1 (also called ARNTL) denotes aryl hydrocarbon receptor nuclear translocator-like protein 1, CLOCK clock circadian regulator, NR1D1 (also called REV-ERBα) nuclear receptor subfamily 1 group D member 1, and ROR retinoic acid receptor–related orphan receptor.