Light-independent role of CRY1 and CRY2 in the mammalian circadian clock.
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.
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, Gene Expression Regulation, Genes, Reporter, Helix-Loop-Helix Motifs, Humans, Intracellular Signaling Peptides and Proteins, Light, Mice, Nuclear Proteins, Period Circadian Proteins, Photoreceptor Cells, Invertebrate, Receptors, G-Protein-Coupled, Trans-Activators, Transcription Factors, Transcriptional Activation, Transfection
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, Gene Expression Regulation, Genes, Reporter, Helix-Loop-Helix Motifs, Humans, Intracellular Signaling Peptides and Proteins, Light, Mice, Nuclear Proteins, Period Circadian Proteins, Photoreceptor Cells, Invertebrate, Receptors, G-Protein-Coupled, Trans-Activators, Transcription Factors, Transcriptional Activation, Transfection
Science
Date: Oct. 22, 1999
PubMed ID: 10531061
View in: Pubmed Google Scholar
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