SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins.
One component of the circadian clock in mammals is the Clock-Bmal1 heterodimeric transcription factor. Among its downstream targets, two genes, Cry1 and Cry2, encode inhibitors of the Clock-Bmal1 complex that establish a negative-feedback loop. We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCF(Fbxl3) ubiquitin ... ligase complex. This regulation by SCF(Fbxl3) is a prerequisite for the efficient and timely reactivation of Clock-Bmal1 and the consequent expression of Per1 and Per2, two regulators of the circadian clock that display tumor suppressor activity. Silencing of Fbxl3 produced no effect in Cry1-/-;Cry2-/- cells, which shows that Fbxl3 controls clock oscillations by mediating the degradation of CRY proteins.
Mesh Terms:
ARNTL Transcription Factors, Animals, Basic Helix-Loop-Helix Transcription Factors, CLOCK Proteins, Cell Cycle Proteins, Cells, Cultured, Circadian Rhythm, Cryptochromes, F-Box Proteins, Flavoproteins, HeLa Cells, Humans, Mice, NIH 3T3 Cells, Nuclear Proteins, Period Circadian Proteins, Promoter Regions, Genetic, RNA Interference, SKP Cullin F-Box Protein Ligases, Trans-Activators, Transcription Factors, Transfection, Ubiquitin
ARNTL Transcription Factors, Animals, Basic Helix-Loop-Helix Transcription Factors, CLOCK Proteins, Cell Cycle Proteins, Cells, Cultured, Circadian Rhythm, Cryptochromes, F-Box Proteins, Flavoproteins, HeLa Cells, Humans, Mice, NIH 3T3 Cells, Nuclear Proteins, Period Circadian Proteins, Promoter Regions, Genetic, RNA Interference, SKP Cullin F-Box Protein Ligases, Trans-Activators, Transcription Factors, Transfection, Ubiquitin
Science
Date: May. 11, 2007
PubMed ID: 17463251
View in: Pubmed Google Scholar
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