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: The widely used proteasome inhibitor MG132 increases the free-running period in a dose-dependent fashion in Ostreococcus . MG132 is a trileucine aldehyde, inhibiting proteasome subunits β1 and β5, but it also targets papain-like cysteine proteases in plants . To verify that modulating the proteasome pathway indeed affects the Ostreococcus free-running period, we analyzed the effects of the highly selective proteasome inhibitor epoxomicin , which inhibits all three catalytic proteasome subunits in plants . Low micromolar concentrations of this drug resulted in robust period increases of ∼9–10 hr (Figure 2A and Figure S2A). Furthermore, an inhibitor (PYR-41)  that acts on the ubiquitin/proteasome pathway via inhibition of ubiquitin-activating enzymes yielded similar, albeit less potent, effects in the lengthening period (Figure 2A and Figure S2B). In combination, the effects of these inhibitors show that targeted protein degradation via the proteasome is indeed necessary to maintain rhythmicity.
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