SCF Fbxl3 Controls the Oscillation of the Circadian Clock by Directing the Degradation of Cryptochrome Proteins
Copyright policy )SCF Fbxl3 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.
- University of Milan Italy
- Florida Southern College United States
- European Institute of Oncology Italy
- Florida State University United States
- New York University United States
SKP Cullin F-Box Protein Ligases, Flavoproteins, F-Box Proteins, ARNTL Transcription Factors, CLOCK Proteins, Nuclear Proteins, Cell Cycle Proteins, Period Circadian Proteins, Circadian Rhythm, Cryptochromes, Mice, Basic Helix-Loop-Helix Transcription Factors, NIH 3T3 Cells, Trans-Activators, Animals, Humans, RNA Interference, Promoter Regions, Genetic, Cells, Cultured, HeLa Cells
SKP Cullin F-Box Protein Ligases, Flavoproteins, F-Box Proteins, ARNTL Transcription Factors, CLOCK Proteins, Nuclear Proteins, Cell Cycle Proteins, Period Circadian Proteins, Circadian Rhythm, Cryptochromes, Mice, Basic Helix-Loop-Helix Transcription Factors, NIH 3T3 Cells, Trans-Activators, Animals, Humans, RNA Interference, Promoter Regions, Genetic, Cells, Cultured, HeLa Cells
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