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Implication of the F-Box Protein FBXL21 in circadian pacemaker function in mammals.


ABSTRACT: In mammals, the circadian clock relies on interlocked feedback loops involving clock genes and their protein products. Post-translational modifications control intracellular trafficking, functionality and degradation of clock proteins and are keys to the functioning of the clock as recently exemplified for the F-Box protein Fbxl3. The SCF(Fbxl3) complex directs degradation of CRY1/2 proteins and Fbxl3 murine mutants have a slower clock. To assess whether the role of Fbxl3 is phylogenetically conserved, we investigated its function in the sheep, a diurnal ungulate. Our data show that Fbxl3 function is conserved and further reveal that its closest homologue, the F-Box protein Fbxl21, also binds to CRY1 which impairs its repressive action towards the transcriptional activators CLOCK/BMAL1. Ho

SUBMITTER: Dardente H 

PROVIDER: S-EPMC2568807 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature