Journal
CELL REPORTS
Volume 23, Issue 8, Pages 2273-2282Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2018.04.064
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Funding
- DrosoClock (ANR)
- ClockGene (ANR)
- FunGenDroso (ANR)
- Equipe FRM (FRM)
- INsecTIME (EU 6th Framework Program)
- INsecTIME (EU 7th Framework Program)
- Ministry for National Economy of Hungary [GINOP-2.3.2-15-2016-00001]
- National Research, Development and Innovation Office [OTKA-PD115404]
- MINECO (FEDER funds) [SAF2013-44782-P]
- INSERM
- EUCLOCK (EU 6th Framework Program)
- EUCLOCK (EU 7th Framework Program)
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Circadian clocks have evolved as time-measuring molecular devices to help organisms adapt their physiology to daily changes in light and temperature. Transcriptional oscillations account for a large fraction of rhythmic protein abundance. However, cycling of various posttranslational modifications, such as ubiquitylation, also contributes to shape the rhythmic protein landscape. In this study, we used an in vivo ubiquitin labeling assay to investigate the circadian ubiquitylated proteome of Drosophila melanogaster. We find that cyclic ubiquitylation affects MEGATOR (MTOR), a chromatin-associated nucleoporin that, in turn, feeds back to regulate the core molecular oscillator. Furthermore, we show that the ubiquitin ligase subunits CULLIN-3 (CUL-3) and SUPERNUMERARY LIMBS (SLMB) cooperate for ubiquitylating the TIMELESS protein. These findings stress the importance of ubiquitylation pathways in the Drosophila circadian clock and reveal a key component of this system.
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