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. 2022 Oct 19;14(20):5116. doi: 10.3390/cancers14205116

Figure 1.

Figure 1

Schematic Representation of the Circadian Clock Transcriptional–Translational Feedback Loops. The main feedback loop is comprised of activator proteins Brain and Muscle ARNT-Like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), and two repressor proteins, Period (PER) and Cryptochrome (CRY). BMAL1 and CLOCK heterodimerize and bind to the E-box, which activates the transcription of CRY (1-2), PER (1-3), RORα, REV-ERBα, and Clock transcription factors (TFs). The primary negative feedback occurs when CRY and PER accumulate and dimerize in the cytoplasm and translocate to the nucleus to inhibit the BMAL1: CLOCK. In the secondary feedback loop, RORα and REV-ERBα activate and inhibit the transcription of BMAL1.