ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2011
Post-translational regulation and nuclear entry of TIMELESS and PERIOD are affected in new timeless mutant.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Post-Translational Modifications in Animal Circadian Clocks.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Chemical biology approaches to study and target circadian clocks and their components.FEBS letters · 2026Review
- Circadian clock genes and insomnia: molecular mechanisms and therapeutic implications.Annals of medicine · 2025Review
- The Function, Regulation, and Mechanism of Protein Turnover in Circadian Systems inInternational journal of molecular sciences · 2024Review
- CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters.PLoS genetics · 2023Article
- Loss of Timeless Underlies an Evolutionary Transition within the Circadian Clock.Molecular biology and evolution · 2022Article
- Evolution of casein kinase 1 and functional analysis of newFrontiers in physiology · 2022Article
- CK2 Inhibits TIMELESS Nuclear Export and Modulates CLOCK Transcriptional Activity to Regulate Circadian Rhythms.Current biology : CB · 2021Article
- O-GlcNAcylation of PERIOD regulates its interaction with CLOCK and timing of circadian transcriptional repression.PLoS genetics · 2019Article
- NewFrontiers in physiology · 2019Article
- CK1α Collaborates with DOUBLETIME to Regulate PERIOD Function in theThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Diurnal protein oscillation profiles in Drosophila head.FEBS letters · 2018Article
- Design Principles of Phosphorylation-Dependent Timekeeping in Eukaryotic Circadian Clocks.Cold Spring Harbor perspectives in biology · 2018Review
- Drosophila TIM binds importin α1, and acts as an adapter to transport PER to the nucleus.PLoS genetics · 2015Article
- A role for timely nuclear translocation of clock repressor proteins in setting circadian clock speed.Experimental neurobiology · 2014Review
- Casein kinase 1 promotes synchrony of the circadian clock network.Molecular and cellular biology · 2014Article
- Speed control: cogs and gears that drive the circadian clock.Trends in neurosciences · 2012Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The molecular circadian clock consists of a feedback loop in which canonical clock proteins negatively regulate transcription of their own genes. Timed nuclear entry of these proteins is critical, but regulation of this event is poorly understood. In Drosophila melanogaster, the idea that nuclear entry of PERIOD (PER) is controlled by its partner protein TIMELESS (TIM) has been challenged by several studies. We identify here a novel mutation in the tim gene that eliminates behavioral rhythms while allowing robust expression of TIM and PER. Mutant TIM can bind to and stabilize PER. However, neither protein is expressed cyclically, and phosphorylation of both is reduced. In addition, TIM and PER are localized in the cytoplasm at all times of day, and mutant TIM attenuates transcriptional feedback by PER in cultured cells, suggesting that it holds PER in the cytoplasm. In fact, much of the reduced phosphorylation of PER in the new tim mutant appears to result from the cytoplasmic localization of PER. Interestingly, mutating a threonine near the original mutation produces similar phenotypes, raising the possibility that defective phosphorylation is the basis of TIM dysfunction in the novel tim mutant. We also show that a stable form of PER is cytoplasmic in tim-null flies. These studies establish an essential role of TIM in the timed nuclear entry of PER.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.