Proteasome function is required for biological timing throughout the twenty-four hour cycle.
Bottom Line: In this study, the Ostreococcus system reveals a central role for targeted protein degradation in the mechanism of circadian timing.TOC1 degradation peaks in response to darkness.Targeted protein degradation, unlike transcription and translation, is shown to be essential to sustain TTFL rhythmicity throughout the circadian cycle.
Affiliation: School of Biological Sciences and Centre for Systems Biology at Edinburgh, University of Edinburgh, The King's Buildings, Mayfield Road, Edinburgh EH9 3JD, UK. firstname.lastname@example.orgShow MeSH
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Mentions: Saturating concentrations of MG132 arrested rhythmic behavior of the CCA1-LUC line (Figure 3A). CCA1-LUC cells entrained in LD12:12 cycles were transferred to constant light at dawn (ZT0), and application of MG132 stopped normal oscillatory behavior. After wash off, the cells directly resumed oscillations (Figure S3A), suggesting that treatment was reversible and largely nontoxic. The delay in phase resulting from treatment pulses followed a direct relation with the duration of the treatment (Figure S3B), suggesting that the circadian pacemaker had paused. The period of the reinitiated rhythm after wash off was not substantially affected (Figure S3C), showing that wash off was efficient and that drug concentration was reduced to insignificant levels. The ability of treated cells to re-entrain was demonstrated by reinstating LD12:12 cycles after 48 hr of constant light (Figure S3A). Altogether, this indicates that when drugs are applied at ZT0, the Ostreococus clock is paused by MG132, and cells reset to wash off.
Affiliation: School of Biological Sciences and Centre for Systems Biology at Edinburgh, University of Edinburgh, The King's Buildings, Mayfield Road, Edinburgh EH9 3JD, UK. email@example.com