The F-box protein Slimb controls the levels of clock proteins Period and Timeless

@article{Grima2002TheFP,
  title={The F-box protein Slimb controls the levels of clock proteins Period and Timeless},
  author={Brigitte Grima and Annie Lamouroux and Elisabeth Chélot and Christian Papin and Bernadette Limbourg-Bouchon and François Rouyer},
  journal={Nature},
  year={2002},
  volume={420},
  pages={178-182}
}
The Drosophila circadian clock is driven by daily fluctuations of the proteins Period and Timeless, which associate in a complex and negatively regulate the transcription of their own genes. Protein phosphorylation has a central role in this feedback loop, by controlling Per stability in both cytoplasmic and nuclear compartments as well as Per/Tim nuclear transfer. However, the pathways regulating degradation of phosphorylated Per and Tim are unknown. Here we show that the product of the slimb… 
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Post-Translational Regulation and Nuclear Entry of TIMELESS and PERIOD Are Affected in New timeless Mutant
TLDR
An essential role of TIM is established in the timed nuclear entry of PER in Drosophila melanogaster by identifying a novel mutation in the tim gene that eliminates behavioral rhythms while allowing robust expression of TIM and PER.
CULLIN-3 Controls TIMELESS Oscillations in the Drosophila Circadian Clock
TLDR
CUL-3 is a new component of the Drosophila clock, which plays an important role in the control of TIM oscillations and shows additive effects on TIM and PER, suggesting different roles for the two ubiquitination complexes on PER and TIM cycling.
The COP9 Signalosome Is Required for Light-Dependent Timeless Degradation and Drosophila Clock Resetting
TLDR
Surprisingly, it is found that manipulations that strongly inhibit CSN activity had minimal effects on circadian rhythms in constant darkness, indicating a specific role for the CSN in light-mediated TIM degradation.
Post-translational regulation of the Drosophila circadian clock requires protein phosphatase 1 (PP1).
TLDR
A modified model for post-translational regulation of the Drosophila clock is proposed, in which PP1 is critical for the rhythmic abundance of TIM/PER while PP2A also regulates the nuclear translocation of tim/PER.
Ribosomal S6 Kinase Cooperates with Casein Kinase 2 to Modulate the Drosophila Circadian Molecular Oscillator
TLDR
It is proposed that the two kinases cooperate within clock neurons to fine-tune circadian period, improving the precision of the clock mechanism.
The Double-Time Protein Kinase Regulates the Subcellular Localization of the Drosophila Clock Protein Period
TLDR
In this study, control of PER subcellular localization in Drosophila clock cells in vivo is examined and it is found that PER can translocate to the nucleus in tim01 null mutants but only if DBT kinase activity is inhibited, and nuclear PER is a potent transcriptional repressor in dbt mutants in vivo without TIM.
Post-translational regulation of the Drosophila circadian clock requires protein phosphatase 1 ( PP 1 )
TLDR
A modified model for post-translational regulation of the Drosophila clock is proposed, in which PP1 is critical for the rhythmic abundance of TIM/PER while PP2A also regulates the nuclear translocation of tim/PER.
Analyzing the degradation of PERIOD protein by the ubiquitin-proteasome pathway in cultured Drosophila cells.
Posttranslational Regulation of Drosophila PERIOD Protein by Protein Phosphatase 2A
Kinetics of Doubletime Kinase-dependent Degradation of the Drosophila Period Protein*
TLDR
The study provides a simple model in which the changes in Drosophila behavioral rhythms can be explained solely by changes in the rate of PER degradation, which resembles that with wild-type DBT.
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References

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TLDR
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