Phosphorylation of CLOCK and BMAL1 —a key regulatory mechanism in the mammalian circadian clockwork

Oct 18, 2025FEBS letters

Phosphorylation of CLOCK and BMAL1 as a key control step in the mammalian body clock

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Abstract

Phosphorylation within the DNA-binding domains of CLOCK and BMAL1 is critical for their inactivation.

  • The CLOCK-BMAL1 complex is essential for regulating circadian rhythms through transcriptional feedback loops.
  • PER and CRY proteins are involved in the repression phase of the CLOCK-BMAL1 complex.
  • Recent studies indicate that phosphorylation may modulate the DNA-binding activity of CLOCK and BMAL1.
  • A proposed 'displacement' model suggests that phosphorylation is key to CLOCK-BMAL1 inactivation.
  • Understanding these mechanisms could provide insights into circadian period regulation.

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