Clock control

The circadian clock is maintained by daily fluctuations in the Period and Timeless proteins that negatively regulate the transcription of their own genes. In the November 14 Nature, Grima et al. describe the mechanism responsible for the phosphorylation-dependent control of Period and Timeless protein degradation in Drosophila (Nature 2002, 420:178-182). Investigation of components of the SCF-mediated ubiquitin proteosome pathway led to the identification of the Slimb protein as an essential cog in the clock within the fly's brain. The Drosophila Slimb gene (Slmb) encodes an F-box/WD40 protein that regulates the levels of different transcription factors. Rescuing the developmental lethality associated with Slmb mutation revealed that adult Slmb mutants were completely arrhythmic under conditions of constant darkness: Period and Timeless oscillations are abolished in constant darkness in the Slmb mutants, and hyperphosphorylated Period protein accumulates. This is the first characterized example of a proteosome degradation protein that regulates the circadian clock.