Light-independent role of CRY1 and CRY2 in the mammalian circadian clock

Science. 1999 Oct 22;286(5440):768-71. doi: 10.1126/science.286.5440.768.

Abstract

Cryptochrome (CRY), a photoreceptor for the circadian clock in Drosophila, binds to the clock component TIM in a light-dependent fashion and blocks its function. In mammals, genetic evidence suggests a role for CRYs within the clock, distinct from hypothetical photoreceptor functions. Mammalian CRY1 and CRY2 are here shown to act as light-independent inhibitors of CLOCK-BMAL1, the activator driving Per1 transcription. CRY1 or CRY2 (or both) showed light-independent interactions with CLOCK and BMAL1, as well as with PER1, PER2, and TIM. Thus, mammalian CRYs act as light-independent components of the circadian clock and probably regulate Per1 transcriptional cycling by contacting both the activator and its feedback inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • ARNTL Transcription Factors
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Biological Clocks*
  • CLOCK Proteins
  • Cell Cycle Proteins
  • Cells, Cultured
  • Circadian Rhythm*
  • Cryptochromes
  • Dimerization
  • Drosophila Proteins*
  • Eye Proteins*
  • Flavoproteins / metabolism
  • Flavoproteins / physiology*
  • Gene Expression Regulation*
  • Genes, Reporter
  • Helix-Loop-Helix Motifs
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Light*
  • Mice
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Period Circadian Proteins
  • Photoreceptor Cells, Invertebrate*
  • Receptors, G-Protein-Coupled
  • Trans-Activators / antagonists & inhibitors
  • Trans-Activators / metabolism
  • Transcription Factors / antagonists & inhibitors
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Transfection

Substances

  • ARNTL Transcription Factors
  • ARNTL protein, human
  • Arntl protein, mouse
  • Basic Helix-Loop-Helix Transcription Factors
  • CRY1 protein, human
  • CRY2 protein, human
  • Cell Cycle Proteins
  • Cry1 protein, mouse
  • Cry2 protein, mouse
  • Cryptochromes
  • Drosophila Proteins
  • Eye Proteins
  • Flavoproteins
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • PER1 protein, human
  • PER2 protein, human
  • Per1 protein, mouse
  • Per2 protein, mouse
  • Period Circadian Proteins
  • Receptors, G-Protein-Coupled
  • TIMELESS protein, human
  • Timeless protein, mouse
  • Trans-Activators
  • Transcription Factors
  • cry protein, Drosophila
  • CLOCK Proteins
  • CLOCK protein, human
  • Clock protein, mouse