Novel Insights into the Regulation of the Timeless Protein
- 27 August 2003
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 23 (21), 7810-7819
- https://doi.org/10.1523/jneurosci.23-21-07810.2003
Abstract
In theDrosophilacircadian clock,period(per) and its partner,timeless(tim), play a central role in the negative limb of an autoregulatory feedback loop. Unlikeper, the dosage of which affects the frequency (tau) of the circadian cycle, we found that increasing copies of thetimgene has no effect on clock period length. The use of thetimpromoter to expressperresults in a shortening of circadian period, also indicating that the regulation oftimis different from that ofper. DrosophilaTIM is similar to the mammalian circadian protein mPER2 in that it shuttles independently between the nucleus and cytoplasm bothin vivoandin vitro. Contrary to the current model that PER and TIM heterodimerization is a prerequisite for their nuclear entry, PER is not required to transport TIM into nuclei, although it influences TIM localization and vice versa. Blocking nuclear export led to increased nuclear expression of TIM in S2 cells and in wild-type andper01larvae, suggesting that PER may be required for nuclear retention of TIM. Unlike PER, nuclear TIM alone has no ability to repress transcription. We propose that TIM drives cycles of PER expression by regulating its stability, and in turn, PER retains TIM in the nucleus, either for the regulation of its own stability or for a novel nuclear role of TIM.Keywords
This publication has 48 references indexed in Scilit:
- Nuclear Export of Mammalian PERIOD ProteinsJournal of Biological Chemistry, 2001
- Regulation of the cycling of timeless (tim) RNAJournal of Neurobiology, 2001
- Post-transcriptional regulation contributes to Drosophila clock gene mRNA cyclingThe EMBO Journal, 1997
- Sex-Specific Assembly of a Dosage Compensation Complex on the Nematode X ChromosomeScience, 1996
- Regulation of Nuclear Entry of the Drosophila Clock Proteins Period and TimelessNeuron, 1996
- Resetting the Drosophila Clock by Photic Regulation of PER and a PER-TIM ComplexScience, 1996
- Regulation of the Drosophila Protein Timeless Suggests a Mechanism for Resetting the Circadian Clock by LightCell, 1996
- A light-entrainment mechanism for the Drosophila circadian clockNature, 1996
- Temporally regulated nuclear entry of the Drosophila period protein contributes to the circadian clockNeuron, 1995
- Block in Nuclear Localization of period Protein by a Second Clock Mutation, timelessScience, 1994