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 Ch{\'e}lot 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…
279 Citations
Post-Translational Regulation and Nuclear Entry of TIMELESS and PERIOD Are Affected in New timeless Mutant
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- 2011
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.
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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
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- 2009
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.
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- BiologyGenes & development
- 2007
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.
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- BiologyThe Journal of Neuroscience
- 2009
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
- BiologyThe Journal of Neuroscience
- 2005
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 )
- Biology
- 2007
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.
- BiologyMethods in enzymology
- 2005
Kinetics of Doubletime Kinase-dependent Degradation of the Drosophila Period Protein*
- BiologyThe Journal of Biological Chemistry
- 2011
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.
References
SHOWING 1-10 OF 61 REFERENCES
Phosphorylation of PERIOD Is Influenced by Cycling Physical Associations of DOUBLE-TIME, PERIOD, and TIMELESS in the Drosophila Clock
- BiologyNeuron
- 2001
A role for the proteasome in the light response of the timeless clock protein.
- BiologyScience
- 1999
The sensitivity of TIM regulation by light was tested and suggested that TIM is degraded through a ubiquitin-proteasome mechanism, and TIM was ubiquitinated in response to light in cultured cells.
Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clock
- BiologyNeuron
- 1995
Regulation of the Drosophila Protein Timeless Suggests a Mechanism for Resetting the Circadian Clock by Light
- BiologyCell
- 1996
Two Novel doubletime Mutants Alter Circadian Properties and Eliminate the Delay between RNA and Protein inDrosophila
- BiologyThe Journal of Neuroscience
- 2000
It is suggested that light and post-transcriptional regulation play major roles in defining the temporal properties of the protein curves and that this lag is unnecessary for the feedback regulation ofper and tim protein on per and tim transcription.
double-time Is a Novel Drosophila Clock Gene that Regulates PERIOD Protein Accumulation
- BiologyCell
- 1998
Light-Induced Degradation of TIMELESS and Entrainment of the Drosophila Circadian Clock
- BiologyScience
- 1996
It is shown that TIM protein may also couple this molecular pacemaker to the environment, because TIM is rapidly degraded after exposure to light.
A light-entrainment mechanism for the Drosophila circadian clock
- BiologyNature
- 1996
The Per–Tim complex is a functional unit of the Drosophila circadian clock, and Tim degradation may be the initial response of the clock to light.