Clk

Summary

Gene Symbol: Clk
Description: Clock
Alias: CG7391, CLK, CLOCK, Dmel\CG7391, Jerk, Jrk, PAS1, bHLHe10, clk, clock, dCLK, dCLK/JRK, dCLOCK, dClck, dClk, dClock, dclk, jrk, clock, CG7391-PA, CG7391-PD, CG7391-PF, CG7391-PG, CG7391-PH, CLOCK, Clk-PA, Clk-PD, Clk-PF, Clk-PG, Clk-PH, dClock
Species: fruit fly
Products:     Clk

Top Publications

  1. Zhao J, Kilman V, Keegan K, Peng Y, Emery P, Rosbash M, et al. Drosophila clock can generate ectopic circadian clocks. Cell. 2003;113:755-66 pubmed
    ..The function of the transcriptional activator, Clock, is necessary in both Drosophila and mammals for the expression of many core clock components...
  2. Benito J, Zheng H, Hardin P. PDP1epsilon functions downstream of the circadian oscillator to mediate behavioral rhythms. J Neurosci. 2007;27:2539-47 pubmed
    The Drosophila circadian oscillator is composed of autoregulatory period/timeless (per/tim) and Clock (Clk) feedback loops that control rhythmic transcription...
  3. Yu W, Houl J, Hardin P. NEMO kinase contributes to core period determination by slowing the pace of the Drosophila circadian oscillator. Curr Biol. 2011;21:756-61 pubmed publisher
    The Drosophila circadian oscillator is comprised of transcriptional feedback loops that are activated by CLOCK (CLK) and CYCLE (CYC) and repressed by PERIOD (PER) and TIMELESS (TIM) [1]...
  4. Smolen P, Hardin P, Lo B, Baxter D, Byrne J. Simulation of Drosophila circadian oscillations, mutations, and light responses by a model with VRI, PDP-1, and CLK. Biophys J. 2004;86:2786-802 pubmed
    ..rhythm generation was developed to represent feedback loops based on transcriptional regulation of per, Clk (dclock), Pdp-1, and vri (vrille)...
  5. Roenneberg T, Merrow M. The network of time: understanding the molecular circadian system. Curr Biol. 2003;13:R198-207 pubmed
    The circadian clock provides a temporal structure that modulates biological functions from the level of gene expression to performance and behaviour...
  6. Blanchard F, Collins B, Cyran S, Hancock D, Taylor M, Blau J. The transcription factor Mef2 is required for normal circadian behavior in Drosophila. J Neurosci. 2010;30:5855-65 pubmed publisher
    ..We found that Mef2 is normally produced in all adult clock neurons and that Mef2 overexpression in clock neurons leads to long period and complex rhythms of adult locomotor ..
  7. Kadener S, Menet J, Schoer R, Rosbash M. Circadian transcription contributes to core period determination in Drosophila. PLoS Biol. 2008;6:e119 pubmed publisher
    The Clock-Cycle (CLK-CYC) heterodimer constitutes a key circadian transcription complex in Drosophila. CYC has a DNA-binding domain but lacks an activation domain...
  8. Abruzzi K, Rodriguez J, Menet J, Desrochers J, Zadina A, Luo W, et al. Drosophila CLOCK target gene characterization: implications for circadian tissue-specific gene expression. Genes Dev. 2011;25:2374-86 pubmed publisher
    b>CLOCK (CLK) is a master transcriptional regulator of the circadian clock in Drosophila...
  9. Sun W, Jeong E, Jeong H, Ko H, Edery I, Kim E. Two distinct modes of PERIOD recruitment onto dCLOCK reveal a novel role for TIMELESS in circadian transcription. J Neurosci. 2010;30:14458-69 pubmed publisher
    ..In Drosophila, the repression of dCLOCK (dCLK)-CYCLE (CYC) transcriptional activity by dPERIOD (dPER) is critical for driving circadian gene expression...

More Information

Publications84

  1. Krupp J, Kent C, Billeter J, Azanchi R, So A, Schonfeld J, et al. Social experience modifies pheromone expression and mating behavior in male Drosophila melanogaster. Curr Biol. 2008;18:1373-83 pubmed publisher
    ..Moreover, levels of these pheromones vary throughout the day in a pattern that depends on the clock genes and most likely also depends on the circadian control of desat1 in the oenocytes...
  2. Scully A, Kay S. Time flies for Drosophila. Cell. 2000;100:297-300 pubmed
  3. Ueda H, Hagiwara M, Kitano H. Robust oscillations within the interlocked feedback model of Drosophila circadian rhythm. J Theor Biol. 2001;210:401-6 pubmed
    ..Glossop, Lyons & Hardin [Science286, 766 (1999)] on Drosophila suggests involvement of another feedback loop by dClk that is interlocked with per-tim feedback loop...
  4. Wu M, Joiner W, Dean T, Yue Z, Smith C, Chen D, et al. SLEEPLESS, a Ly-6/neurotoxin family member, regulates the levels, localization and activity of Shaker. Nat Neurosci. 2010;13:69-75 pubmed publisher
    ..SSS is predicted to belong to the Ly-6/neurotoxin superfamily, suggesting a mechanism for regulation of neuronal excitability by endogenous toxin-like molecules. ..
  5. Yu W, Zheng H, Houl J, Dauwalder B, Hardin P. PER-dependent rhythms in CLK phosphorylation and E-box binding regulate circadian transcription. Genes Dev. 2006;20:723-33 pubmed
    Transcriptional activation by CLOCK-CYCLE (CLK-CYC) heterodimers and repression by PERIOD-TIMELESS (PER-TIM) heterodimers are essential for circadian oscillator function in Drosophila...
  6. Luo W, Li Y, Tang C, Abruzzi K, Rodriguez J, Pescatore S, et al. CLOCK deubiquitylation by USP8 inhibits CLK/CYC transcription in Drosophila. Genes Dev. 2012;26:2536-49 pubmed publisher
    ..In Drosophila, the transcription factors CLOCK (CLK) and CYCLE (CYC) activate the transcription of direct target genes like period (per) and timeless (tim)...
  7. Lin Y, Han M, Shimada B, Wang L, Gibler T, Amarakone A, et al. Influence of the period-dependent circadian clock on diurnal, circadian, and aperiodic gene expression in Drosophila melanogaster. Proc Natl Acad Sci U S A. 2002;99:9562-7 pubmed
    ..Thus, the period-dependent circadian clock regulates only a limited set of rhythmically expressed transcripts...
  8. Kloss B, Rothenfluh A, Young M, Saez L. Phosphorylation of period is influenced by cycling physical associations of double-time, period, and timeless in the Drosophila clock. Neuron. 2001;30:699-706 pubmed
    ..Whereas the period (per), timeless (tim), and dClock (dClk) genes of Drosophila each contribute cycling mRNA and protein to a circadian clock, dbt RNA and DBT protein ..
  9. Sarov Blat L, So W, Liu L, Rosbash M. The Drosophila takeout gene is a novel molecular link between circadian rhythms and feeding behavior. Cell. 2000;101:647-56 pubmed
    We report the characterization of a novel Drosophila circadian clock-regulated output gene, takeout (to). The to amino acid sequence shows similarity to two ligand binding proteins, including juvenile hormone binding protein...
  10. Hardin P. The circadian timekeeping system of Drosophila. Curr Biol. 2005;15:R714-22 pubmed
    ..I will also discuss where work remains to be done to give a comprehensive picture of the circadian clock in Drosophila and likely many other organisms.
  11. Garbe D, Fang Y, Zheng X, Sowcik M, Anjum R, Gygi S, et al. Cooperative interaction between phosphorylation sites on PERIOD maintains circadian period in Drosophila. PLoS Genet. 2013;9:e1003749 pubmed publisher
    Circadian rhythms in Drosophila rely on cyclic regulation of the period (per) and timeless (tim) clock genes...
  12. Tanoue S, Krishnan P, Krishnan B, Dryer S, Hardin P. Circadian clocks in antennal neurons are necessary and sufficient for olfaction rhythms in Drosophila. Curr Biol. 2004;14:638-49 pubmed
    The Drosophila circadian clock is controlled by interlocked transcriptional feedback loops that operate in many neuronal and nonneuronal tissues...
  13. Ceriani M, Darlington T, Staknis D, Mas P, Petti A, Weitz C, et al. Light-dependent sequestration of TIMELESS by CRYPTOCHROME. Science. 1999;285:553-6 pubmed
    ..Thus, CRY acts as a circadian photoreceptor by directly interacting with core components of the circadian clock.
  14. Smolen P, Baxter D, Byrne J. A reduced model clarifies the role of feedback loops and time delays in the Drosophila circadian oscillator. Biophys J. 2002;83:2349-59 pubmed
    ..A negative feedback loop is included, in which PER protein represses per transcription by binding the dCLOCK transcription factor...
  15. Lim C, Lee J, Choi C, Kim J, Doh E, Choe J. Functional role of CREB-binding protein in the circadian clock system of Drosophila melanogaster. Mol Cell Biol. 2007;27:4876-90 pubmed
    Rhythmic histone acetylation underlies the oscillating expression of clock genes in the mammalian circadian clock system...
  16. Smolen P, Baxter D, Byrne J. Modeling circadian oscillations with interlocking positive and negative feedback loops. J Neurosci. 2001;21:6644-56 pubmed
    ..quot; PER suppresses its own transcription by binding to the transcriptional regulator dCLOCK, thus yielding negative feedback...
  17. Keene A, Duboué E, McDonald D, Dus M, Suh G, Waddell S, et al. Clock and cycle limit starvation-induced sleep loss in Drosophila. Curr Biol. 2010;20:1209-15 pubmed publisher
    ..The circadian clock genes Clock (Clk) and cycle (cyc) are critical for proper sleep suppression during starvation...
  18. Wijnen H, Naef F, Young M. Molecular and statistical tools for circadian transcript profiling. Methods Enzymol. 2005;393:341-65 pubmed
    ..Both comparative and temporal study designs are discussed, and their use in circadian research is illustrated with examples. Data analysis methods to assess periodic components in time series data are outlined in detail. ..
  19. Hung H, Maurer C, Zorn D, Chang W, Weber F. Sequential and compartment-specific phosphorylation controls the life cycle of the circadian CLOCK protein. J Biol Chem. 2009;284:23734-42 pubmed publisher
    The circadian clock facilitates a temporal coordination of most homeostatic activities and their synchronization with the environmental cycles of day and night...
  20. Glossop N, Houl J, Zheng H, Ng F, Dudek S, Hardin P. VRILLE feeds back to control circadian transcription of Clock in the Drosophila circadian oscillator. Neuron. 2003;37:249-61 pubmed
    The Drosophila circadian oscillator consists of interlocked period (per)/timeless (tim) and Clock (Clk) transcriptional/translational feedback loops...
  21. Kim E, Edery I. Balance between DBT/CKIepsilon kinase and protein phosphatase activities regulate phosphorylation and stability of Drosophila CLOCK protein. Proc Natl Acad Sci U S A. 2006;103:6178-83 pubmed
    ..A negative feedback loop wherein PER directly inhibits the transcriptional activity of the CLOCK-CYCLE (CLK-CYC) heterodimer is central to the generation of molecular rhythms and normal progression of the clock ..
  22. Bywalez W, Menegazzi P, Rieger D, Schmid B, Helfrich Forster C, Yoshii T. The dual-oscillator system of Drosophila melanogaster under natural-like temperature cycles. Chronobiol Int. 2012;29:395-407 pubmed publisher
    ..The bimodal activity rhythm was absent in the circadian clock mutants Clk(Jrk) and cyc(01) and reduced in per(01) and tim(01) mutants...
  23. McDonald M, Rosbash M, Emery P. Wild-type circadian rhythmicity is dependent on closely spaced E boxes in the Drosophila timeless promoter. Mol Cell Biol. 2001;21:1207-17 pubmed
    ..elements close to the canonical E box, which can also be transactivated by the circadian transcription factor dCLOCK. These E-box-like sequences cooperate with the canonical E-box element to promote high-amplitude transcription, ..
  24. Busza A, Murad A, Emery P. Interactions between circadian neurons control temperature synchronization of Drosophila behavior. J Neurosci. 2007;27:10722-33 pubmed
    ..In conclusion, the behavioral responses to temperature input are determined by both the individual properties of specific groups of circadian neurons and their organization in a neural network. ..
  25. Yu W, Zheng H, Price J, Hardin P. DOUBLETIME plays a noncatalytic role to mediate CLOCK phosphorylation and repress CLOCK-dependent transcription within the Drosophila circadian clock. Mol Cell Biol. 2009;29:1452-8 pubmed publisher
    ..Within the Drosophila melanogaster circadian clock, DOUBLETIME (DBT) kinase is necessary for the phosphorylation of PERIOD (PER), a transcriptional repressor, and ..
  26. Glossop N, Lyons L, Hardin P. Interlocked feedback loops within the Drosophila circadian oscillator. Science. 1999;286:766-8 pubmed
    Drosophila Clock (dClk) is rhythmically expressed, with peaks in mRNA and protein (dCLK) abundance early in the morning...
  27. Kadener S, Menet J, Sugino K, Horwich M, Weissbein U, Nawathean P, et al. A role for microRNAs in the Drosophila circadian clock. Genes Dev. 2009;23:2179-91 pubmed publisher
    ..They included three core clock mRNAs-clock (clk), vrille (vri), and clockworkorange (cwo)...
  28. Bae K, Lee C, Sidote D, Chuang K, Edery I. Circadian regulation of a Drosophila homolog of the mammalian Clock gene: PER and TIM function as positive regulators. Mol Cell Biol. 1998;18:6142-51 pubmed
    ..Science 280:1599-1603, 1998.) Transcripts from this putative Clock ortholog (designated dClock) undergo daily rhythms in abundance that are antiphase to the cycling observed for the RNA products from the ..
  29. Hung H, Maurer C, Kay S, Weber F. Circadian transcription depends on limiting amounts of the transcription co-activator nejire/CBP. J Biol Chem. 2007;282:31349-57 pubmed
    The circadian clock orchestrates physiological and behavioral activities, including metabolism, neuronal activity, and cell proliferation in synchrony with the environmental cycle of day and night...
  30. Leloup -, Goldbeter -. Chaos and birhythmicity in a model for circadian oscillations of the PER and TIM proteins in drosophila. J Theor Biol. 1999;198:445-59 pubmed
    ..Beyond the particular context of circadian rhythms we discuss the results in the light of other mechanisms underlying chaos and birhythmicity in regulated biological systems. Copyright 1999 Academic Press. ..
  31. Lear B, Zhang L, Allada R. The neuropeptide PDF acts directly on evening pacemaker neurons to regulate multiple features of circadian behavior. PLoS Biol. 2009;7:e1000154 pubmed publisher
    Discrete clusters of circadian clock neurons temporally organize daily behaviors such as sleep and wake. In Drosophila, a network of just 150 neurons drives two peaks of timed activity in the morning and evening...
  32. Zhang L, Chung B, Lear B, Kilman V, Liu Y, Mahesh G, et al. DN1(p) circadian neurons coordinate acute light and PDF inputs to produce robust daily behavior in Drosophila. Curr Biol. 2010;20:591-9 pubmed publisher
    ..The fruit fly Drosophila exhibits clock-driven activity increases that anticipate dawn and dusk and free-running rhythms under constant conditions...
  33. Darlington T, Wager Smith K, Ceriani M, Staknis D, Gekakis N, Steeves T, et al. Closing the circadian loop: CLOCK-induced transcription of its own inhibitors per and tim. Science. 1998;280:1599-603 pubmed
    ..b>dCLOCK functioned as a heterodimer with a Drosophila homolog of BMAL1...
  34. Collins B, Rosato E, Kyriacou C. Seasonal behavior in Drosophila melanogaster requires the photoreceptors, the circadian clock, and phospholipase C. Proc Natl Acad Sci U S A. 2004;101:1945-50 pubmed
    ..is observed, requiring the light input received through the visual system during the day and the circadian clock at night...
  35. Kumar S, Chen D, Sehgal A. Dopamine acts through Cryptochrome to promote acute arousal in Drosophila. Genes Dev. 2012;26:1224-34 pubmed publisher
    The fruit fly, Drosophila melanogaster, is generally diurnal, but a few mutant strains, such as the circadian clock mutant Clk(Jrk), have been described as nocturnal...
  36. Lee C, Bae K, Edery I. PER and TIM inhibit the DNA binding activity of a Drosophila CLOCK-CYC/dBMAL1 heterodimer without disrupting formation of the heterodimer: a basis for circadian transcription. Mol Cell Biol. 1999;19:5316-25 pubmed
    The Drosophila CLOCK (dCLOCK) and CYCLE (CYC) (also referred to as dBMAL1) proteins are members of the basic helix-loop-helix PAS (PER-ARNT-SIM) superfamily of transcription factors and are required for high-level expression of the ..
  37. Szabó A, Papin C, Zorn D, Ponien P, Weber F, Raabe T, et al. The CK2 kinase stabilizes CLOCK and represses its activity in the Drosophila circadian oscillator. PLoS Biol. 2013;11:e1001645 pubmed publisher
    ..the CK2 kinase phosphorylates and destabilizes the PERIOD (PER) and TIMELESS (TIM) proteins, which inhibit CLOCK (CLK) transcriptional activity. Here we show that CK2 also targets the CLK activator directly...
  38. Richier B, Michard Vanhée C, Lamouroux A, Papin C, Rouyer F. The clockwork orange Drosophila protein functions as both an activator and a repressor of clock gene expression. J Biol Rhythms. 2008;23:103-16 pubmed publisher
    The Drosophila clock relies on transcriptional feedback loops that generate daily oscillations of the clock gene expression at mRNA and protein levels...
  39. Gummadova J, Coutts G, Glossop N. Analysis of the Drosophila Clock promoter reveals heterogeneity in expression between subgroups of central oscillator cells and identifies a novel enhancer region. J Biol Rhythms. 2009;24:353-67 pubmed publisher
    The CLOCK-CYCLE (CLK-CYC) heterodimer lies at the heart of the circadian oscillator mechanism in Drosophila, yet little is known about the identity of transcription factors that regulate the expression of Clk and/or cyc...
  40. Kaneko M. Neural substrates of Drosophila rhythms revealed by mutants and molecular manipulations. Curr Opin Neurobiol. 1998;8:652-8 pubmed
    In the fruit-fly Drosophila, rhythmic expression of the clock gene period is detected in cells throughout the body...
  41. Kaneko M, Hall J. Neuroanatomy of cells expressing clock genes in Drosophila: transgenic manipulation of the period and timeless genes to mark the perikarya of circadian pacemaker neurons and their projections. J Comp Neurol. 2000;422:66-94 pubmed
    Subsets of brain neurons expressing the clock genes period (per) and timeless (tim) are involved in the generation of circadian behavioral rhythms...
  42. Hendricks J, Lu S, Kume K, Yin J, Yang Z, Sehgal A. Gender dimorphism in the role of cycle (BMAL1) in rest, rest regulation, and longevity in Drosophila melanogaster. J Biol Rhythms. 2003;18:12-25 pubmed
    The central clock is generally thought to provide timing information for rest/activity but not to otherwise participate in regulation of these states...
  43. Lim C, Chung B, Pitman J, McGill J, Pradhan S, Lee J, et al. Clockwork orange encodes a transcriptional repressor important for circadian-clock amplitude in Drosophila. Curr Biol. 2007;17:1082-9 pubmed
    ..In Drosophila, the basic helix-loop helix (bHLH)-PAS transcription-factor heterodimer, CLOCK/CYCLE (CLK/CYC), transcriptionally activates the clock components period (per), timeless (tim), Par domain protein ..
  44. Blau J, Young M. Cycling vrille expression is required for a functional Drosophila clock. Cell. 1999;99:661-71 pubmed
    ..vri RNA levels oscillate with a circadian rhythm. Cycling is directly regulated by the transcription factors dCLOCK and CYCLE, which are also required for oscillations of period and timeless RNA...
  45. Fathallah Shaykh H, Bona J, Kadener S. Mathematical model of the Drosophila circadian clock: loop regulation and transcriptional integration. Biophys J. 2009;97:2399-408 pubmed publisher
    Eukaryotic circadian clocks include interconnected positive and negative feedback loops. The clock-cycle dimer (CLK-CYC) and its homolog, CLK-BMAL1, are key transcriptional activators of central components of the Drosophila and mammalian ..
  46. Cyran S, Buchsbaum A, Reddy K, Lin M, Glossop N, Hardin P, et al. vrille, Pdp1, and dClock form a second feedback loop in the Drosophila circadian clock. Cell. 2003;112:329-41 pubmed
    The Drosophila circadian clock consists of two interlocked transcriptional feedback loops. In one loop, dCLOCK/CYCLE activates period expression, and PERIOD protein then inhibits dCLOCK/CYCLE activity...
  47. Dunlap J. Molecular bases for circadian clocks. Cell. 1999;96:271-90 pubmed
  48. Lee G, Bahn J, Park J. Sex- and clock-controlled expression of the neuropeptide F gene in Drosophila. Proc Natl Acad Sci U S A. 2006;103:12580-5 pubmed
    ..Interestingly, one of the ms-npf neuronal groups belongs to the previously defined clock-controlling dorsolateral neurons...
  49. Leloup J, Goldbeter A. Modeling the molecular regulatory mechanism of circadian rhythms in Drosophila. Bioessays. 2000;22:84-93 pubmed
    ..closely related to experimental observations can be considered for the regulatory mechanism of the circadian clock in this organism...
  50. Luo W, Sehgal A. Regulation of circadian behavioral output via a MicroRNA-JAK/STAT circuit. Cell. 2012;148:765-79 pubmed publisher
    Although molecular components of the circadian clock are known, mechanisms that transmit signals from the clock and produce rhythmic behavior are poorly understood...
  51. Li Q, Lang X. Internal noise-sustained circadian rhythms in a Drosophila model. Biophys J. 2008;94:1983-94 pubmed
    ..It is found that the time delay could efficiently tune the performance of the noise-sustained oscillations. These results might aid understanding of the exploitation of intracellular noise in biochemical and genetic regulatory systems. ..
  52. Shaw P, Tononi G, Greenspan R, Robinson D. Stress response genes protect against lethal effects of sleep deprivation in Drosophila. Nature. 2002;417:287-91 pubmed
    ..homeostatic and circadian processes in Drosophila, we examined homeostasis in the canonical loss-of-function clock mutants period (per(01)), timeless (tim(01)), clock (Clk(jrk)) and cycle (cyc(01))...
  53. Hastings M, Maywood E. Circadian clocks in the mammalian brain. Bioessays. 2000;22:23-31 pubmed
    ..e. circadian. In mammals, the circadian clock governing activity/ rest, neuroendocrine and autonomic rhythms lies in the hypothalamus, in the suprachiasmatic ..
  54. Houl J, Ng F, Taylor P, Hardin P. CLOCK expression identifies developing circadian oscillator neurons in the brains of Drosophila embryos. BMC Neurosci. 2008;9:119 pubmed publisher
    The Drosophila circadian oscillator is composed of transcriptional feedback loops in which CLOCK-CYCLE (CLK-CYC) heterodimers activate their feedback regulators period (per) and timeless (tim) via E-box mediated transcription...
  55. Brown S, Schibler U. The ins and outs of circadian timekeeping. Curr Opin Genet Dev. 1999;9:588-94 pubmed
    ..Though light perception by the central clock is ocular in mammals, it probably proceeds via a mechanism separate from traditional visual transduction...
  56. Allada R. Circadian clocks: a tale of two feedback loops. Cell. 2003;112:284-6 pubmed
    ..In Drosophila, the first loop has been well characterized and controls rhythmic period expression. In this issue of Cell, define a role for a transcriptional activator and a repressor in the second feedback loop. ..
  57. Allada R, Kadener S, Nandakumar N, Rosbash M. A recessive mutant of Drosophila Clock reveals a role in circadian rhythm amplitude. EMBO J. 2003;22:3367-75 pubmed
    The transcription factor Clock (Clk) plays a critical role in animal circadian rhythms. Genetic studies defining its function have relied on two dominant negative alleles, one in Drosophila and one in mice...
  58. Allada R, White N, So W, Hall J, Rosbash M. A mutant Drosophila homolog of mammalian Clock disrupts circadian rhythms and transcription of period and timeless. Cell. 1998;93:791-804 pubmed
    We report the identification, characterization, and cloning of a novel Drosophila circadian rhythm gene, dClock. The mutant, initially called Jrk, manifests dominant effects: heterozygous flies have a period alteration and half are ..
  59. Menet J, Abruzzi K, Desrochers J, Rodriguez J, Rosbash M. Dynamic PER repression mechanisms in the Drosophila circadian clock: from on-DNA to off-DNA. Genes Dev. 2010;24:358-67 pubmed publisher
    ..here in the Drosophila model two different mechanisms by which the circadian repressor PERIOD (PER) inhibits CLOCK/CYCLE (CLK/CYC)-mediated transcription...
  60. Xu K, Zheng X, Sehgal A. Regulation of feeding and metabolism by neuronal and peripheral clocks in Drosophila. Cell Metab. 2008;8:289-300 pubmed publisher
    ..In Drosophila, clock proteins are expressed in many metabolically important tissues but have not been linked to metabolic processes...
  61. Park J, Helfrich Forster C, Lee G, Liu L, Rosbash M, Hall J. Differential regulation of circadian pacemaker output by separate clock genes in Drosophila. Proc Natl Acad Sci U S A. 2000;97:3608-13 pubmed
    Regulation of the Drosophila pigment-dispersing factor (pdf) gene products was analyzed in wild-type and clock mutants...
  62. Chen W, Majercak J, Edery I. Clock-gated photic stimulation of timeless expression at cold temperatures and seasonal adaptation in Drosophila. J Biol Rhythms. 2006;21:256-71 pubmed
    Numerous lines of evidence indicate that the initial photoresponse of the circadian clock in Drosophila melanogaster is the light-induced degradation of TIMELESS (TIM)...
  63. Chang D, Reppert S. A novel C-terminal domain of drosophila PERIOD inhibits dCLOCK:CYCLE-mediated transcription. Curr Biol. 2003;13:758-62 pubmed
    ..PERIOD (PER) and TIMELESS (TIM) inhibit their own transcription by association with the transcriptional activators dCLOCK (dCLK) and CYCLE (CYC)...
  64. Beaver L, Giebultowicz J. Regulation of copulation duration by period and timeless in Drosophila melanogaster. Curr Biol. 2004;14:1492-7 pubmed
    The circadian clock involves several clock genes encoding interacting transcriptional regulators...
  65. Wu M, Koh K, Yue Z, Joiner W, Sehgal A. A genetic screen for sleep and circadian mutants reveals mechanisms underlying regulation of sleep in Drosophila. Sleep. 2008;31:465-72 pubmed
    ..Our data suggest that most short-sleeping mutant phenotypes in Drosophila are characterized by an inability to stay asleep, most likely because of a reduced arousal threshold. ..
  66. Bae K, Lee C, Hardin P, Edery I. dCLOCK is present in limiting amounts and likely mediates daily interactions between the dCLOCK-CYC transcription factor and the PER-TIM complex. J Neurosci. 2000;20:1746-53 pubmed
    In Drosophila melanogaster four circadian clock proteins termed PERIOD (PER), TIMELESS (TIM), dCLOCK (dCLK), and CYCLE (CYC/dBMAL1) function in a transcriptional feedback loop that is a core element of the oscillator mechanism...
  67. Yoshii T, Sakamoto M, Tomioka K. A temperature-dependent timing mechanism is involved in the circadian system that drives locomotor rhythms in the fruit fly Drosophila melanogaster. Zoolog Sci. 2002;19:841-50 pubmed
    The circadian clock of Drosophila melanogaster is thought to include rhythmic expression of period gene. Recent studies suggested, however, that a per-less oscillation is also involved in the regulation of circadian locomotor rhythms...
  68. Lim C, Lee J, Choi C, Kilman V, Kim J, Park S, et al. The novel gene twenty-four defines a critical translational step in the Drosophila clock. Nature. 2011;470:399-403 pubmed publisher
    ..Weak rhythms are accompanied by marked reductions in the levels of the clock protein Period (PER) as well as more modest effects on Timeless (TIM)...
  69. Kula Eversole E, Nagoshi E, Shang Y, Rodriguez J, Allada R, Rosbash M. Surprising gene expression patterns within and between PDF-containing circadian neurons in Drosophila. Proc Natl Acad Sci U S A. 2010;107:13497-502 pubmed publisher
    ..Although half of the l-LNv-enriched mRNA population, including core clock mRNAs, is shared between the l-LNvs and s-LNvs, the other half is l-LNv- and s-LNv-specific...
  70. Yoshii T, Heshiki Y, Ibuki Ishibashi T, Matsumoto A, Tanimura T, Tomioka K. Temperature cycles drive Drosophila circadian oscillation in constant light that otherwise induces behavioural arrhythmicity. Eur J Neurosci. 2005;22:1176-84 pubmed
    ..cycles to establish a steady-state entrainment, suggesting that the rhythm is endogenous and driven by a circadian clock. Western blot analysis revealed that PER and TIM increased during the cryophase, peaking at the middle to late ..
  71. Ashmore L, Sathyanarayanan S, Silvestre D, Emerson M, Schotland P, Sehgal A. Novel insights into the regulation of the timeless protein. J Neurosci. 2003;23:7810-9 pubmed
    In the Drosophila circadian clock, period (per) and its partner, timeless (tim), play a central role in the negative limb of an autoregulatory feedback loop...
  72. Ling J, Dubruille R, Emery P. KAYAK-? modulates circadian transcriptional feedback loops in Drosophila pacemaker neurons. J Neurosci. 2012;32:16959-70 pubmed publisher
    ..In Drosophila, the dimeric transcription factor CLOCK/CYCLE (CLK/CYC) promotes period (per), timeless (tim), vrille (vri), and PAR-domain protein 1 (Pdp1) transcription...
  73. Matsumoto A, Ukai Tadenuma M, Yamada R, Houl J, Uno K, Kasukawa T, et al. A functional genomics strategy reveals clockwork orange as a transcriptional regulator in the Drosophila circadian clock. Genes Dev. 2007;21:1687-700 pubmed
    The Drosophila circadian clock consists of integrated autoregulatory feedback loops, making the clock difficult to elucidate without comprehensively identifying the network components in vivo...
  74. Lamaze A, Lamouroux A, Vias C, Hung H, Weber F, Rouyer F. The E3 ubiquitin ligase CTRIP controls CLOCK levels and PERIOD oscillations in Drosophila. EMBO Rep. 2011;12:549-57 pubmed publisher
    In the Drosophila circadian clock, the CLOCK/CYCLE complex activates the period and timeless genes that negatively feedback on CLOCK/CYCLE activity. The 24-h pace of this cycle depends on the stability of the clock proteins...
  75. Yildiz O, Doi M, Yujnovsky I, Cardone L, Berndt A, Hennig S, et al. Crystal structure and interactions of the PAS repeat region of the Drosophila clock protein PERIOD. Mol Cell. 2005;17:69-82 pubmed publisher
    PERIOD proteins are central components of the Drosophila and mammalian circadian clock. Their function is controlled by daily changes in synthesis, cellular localization, phosphorylation, degradation, as well as specific interactions ..