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
-
BMAL1 protein, human
-
Bmal1 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