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    Clk Clock [ Drosophila melanogaster (fruit fly) ]

    Gene ID: 38872, updated on 17-Dec-2024

    GeneRIFs: Gene References Into Functions

    GeneRIFPubMed TitleDate
    CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters.

    CLOCK and TIMELESS regulate rhythmic occupancy of the BRAHMA chromatin-remodeling protein at clock gene promoters.
    Tabuloc CA, Cai YD, Kwok RS, Chan EC, Hidalgo S, Chiu JC., Free PMC Article

    03/8/2023
    Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms.

    Clock proteins regulate spatiotemporal organization of clock genes to control circadian rhythms.
    Xiao Y, Yuan Y, Jimenez M, Soni N, Yadlapalli S., Free PMC Article

    12/4/2021
    Circadian and Genetic Modulation of Visually-Guided Navigation in Drosophila Larvae.

    Circadian and Genetic Modulation of Visually-Guided Navigation in Drosophila Larvae.
    Asirim EZ, Humberg TH, Maier GL, Sprecher SG., Free PMC Article

    11/21/2020
    Study finds that AMP-activated protein kinase (SNF4Agamma) regulates circadian rhythm by affecting CLOCK in drosophila. Study shows that the AMPKgamma subunit of AMPK, a central regulator of cellular metabolism, copurifies with the CLK/CYC complex in Drosophila S2 cells.

    AMP-Activated Protein Kinase Regulates Circadian Rhythm by Affecting CLOCK in Drosophila.
    Cho E, Kwon M, Jung J, Kang DH, Jin S, Choi SE, Kang Y, Kim EY., Free PMC Article

    06/13/2020
    Data suggest that the clock genes PERIOD and TIMELESS in peripheral clocks show reduction in both expression level and rhythmicity with age.

    Clock gene expression and locomotor activity predict death in the last days of life in Drosophila melanogaster.
    Zhao J, Warman GR, Cheeseman JF., Free PMC Article

    11/2/2019
    Spliceosome factors target tim mRNA to control clock protein accumulation and circadian behavior in Drosophila.

    Spliceosome factors target timeless (tim) mRNA to control clock protein accumulation and circadian behavior in Drosophila.
    Shakhmantsir I, Nayak S, Grant GR, Sehgal A., Free PMC Article

    03/16/2019
    In vivo functional characterization of PER O-GlcNAcylation sites indicates that O-GlcNAcylation at PER(S942) reduces interactions between PER and CLOCK (CLK), the key transcriptional activator of clock-controlled genes

    O-GlcNAcylation of PERIOD regulates its interaction with CLOCK and timing of circadian transcriptional repression.
    Li YH, Liu X, Vanselow JT, Zheng H, Schlosser A, Chiu JC., Free PMC Article

    03/16/2019
    experiments define the genetic architecture required to initiate circadian clock function in Drosophila, reveal mechanisms governing circadian activator stability that are conserved in perhaps all eukaryotes, and suggest that Clk, cyc, and cry expression is sufficient to drive clock expression in naive cells

    CLOCK stabilizes CYCLE to initiate clock function in Drosophila.
    Liu T, Mahesh G, Yu W, Hardin PE., Free PMC Article

    06/30/2018
    propose that the dCLK/CYC-controlled TTFL operates differently in subsets of pacemaker neurons, which may contribute to their specific functions

    Pacemaker-neuron-dependent disturbance of the molecular clockwork by a Drosophila CLOCK mutant homologous to the mouse Clock mutation.
    Lee E, Cho E, Kang DH, Jeong EH, Chen Z, Yoo SH, Kim EY., Free PMC Article

    01/27/2018
    ClkAR mutants showed significantly faster age-related locomotor deficits. Accelerated locomotor decline of the ClkAR mutant required expression of the PDF receptor and correlated to an apparent loss of dopaminergic neurons in the brain

    Drosophila Clock Is Required in Brain Pacemaker Neurons to Prevent Premature Locomotor Aging Independently of Its Circadian Function.
    Vaccaro A, Issa AR, Seugnet L, Birman S, Klarsfeld A., Free PMC Article

    05/27/2017
    Here we demonstrate that the transcription factor CLOCKWORK ORANGE (CWO) antagonizes CLK-CYC E-box binding, thus enhancing the removal of CLK-CYC from E-boxes to maintain transcriptional repression. This process requires PER, which suggests that PER-TIM and CWO cooperate to maintain a transcriptionally repressed state by removing CLK-CYC from E-boxes

    CLOCKWORK ORANGE Enhances PERIOD Mediated Rhythms in Transcriptional Repression by Antagonizing E-box Binding by CLOCK-CYCLE.
    Zhou J, Yu W, Hardin PE., Free PMC Article

    05/6/2017
    these results demonstrate a key role of Clk post-transcriptional control in stabilizing circadian transcription.

    Clk post-transcriptional control denoises circadian transcription both temporally and spatially.
    Lerner I, Bartok O, Wolfson V, Menet JS, Weissbein U, Afik S, Haimovich D, Gafni C, Friedman N, Rosbash M, Kadener S., Free PMC Article

    03/5/2016
    Our findings suggest a novel role for clock protein phosphorylation in governing the relative strengths of entraining modalities by adjusting the dynamics of circadian gene expression.

    Phosphorylation of a central clock transcription factor is required for thermal but not photic entrainment.
    Lee E, Jeong EH, Jeong HJ, Yildirim E, Vanselow JT, Ng F, Liu Y, Mahesh G, Kramer A, Hardin PE, Edery I, Kim EY., Free PMC Article

    11/7/2015
    These results demonstrate that CLK phosphorylation influences the circadian period by regulating CLK activity and progression through the feedback loop.

    Phosphorylation of the transcription activator CLOCK regulates progression through a ∼ 24-h feedback loop to influence the circadian period in Drosophila.
    Mahesh G, Jeong E, Ng FS, Liu Y, Gunawardhana K, Houl JH, Yildirim E, Amunugama R, Jones R, Allen DL, Edery I, Kim EY, Hardin PE., Free PMC Article

    10/4/2014
    Computational dissection of CLK/CYC context-specific binding sites reveals sequence motifs for putative partner factors, which are predictive for individual binding sites

    cis-regulatory requirements for tissue-specific programs of the circadian clock.
    Meireles-Filho ACA, Bardet AF, Yáñez-Cuna JO, Stampfel G, Stark A.

    08/23/2014
    usp8 loss of function (RNAi) or expression of a dominant-negative form of the protein (USP8-DN) enhances CLK/CYC transcriptional activity and alters fly locomotor activity rhythms

    CLOCK deubiquitylation by USP8 inhibits CLK/CYC transcription in Drosophila.
    Luo W, Li Y, Tang CH, Abruzzi KC, Rodriguez J, Pescatore S, Rosbash M., Free PMC Article

    01/26/2013
    CLK has specific targets in different tissues, implying that important CLK partner proteins and/or mechanisms contribute to gene-specific and tissue-specific regulation

    Drosophila CLOCK target gene characterization: implications for circadian tissue-specific gene expression.
    Abruzzi KC, Rodriguez J, Menet JS, Desrochers J, Zadina A, Luo W, Tkachev S, Rosbash M., Free PMC Article

    12/24/2011
    CTRIP destabilizes CLK protein in a PER-independent manner and helps degradation of phosphorylated PER and TIM in the morning

    The E3 ubiquitin ligase CTRIP controls CLOCK levels and PERIOD oscillations in Drosophila.
    Lamaze A, Lamouroux A, Vias C, Hung HC, Weber F, Rouyer F., Free PMC Article

    09/17/2011
    dPER(DeltaCBD) does not provoke the daily hyperphosphorylation of dCLOCK, indicating that direct interactions between dPER and dCLOCK are necessary for the dCLOCK phosphorylation

    Two distinct modes of PERIOD recruitment onto dCLOCK reveal a novel role for TIMELESS in circadian transcription.
    Sun WC, Jeong EH, Jeong HJ, Ko HW, Edery I, Kim EY., Free PMC Article

    12/4/2010
    findings show that Clk and cyc act during starvation to modulate the conflict of whether flies sleep or search for food

    Clock and cycle limit starvation-induced sleep loss in Drosophila.
    Keene AC, Duboué ER, McDonald DM, Dus M, Suh GS, Waddell S, Blau J., Free PMC Article

    11/6/2010
    Results reveal clear heterogeneity in Clock gene expression in the brain and provide a necessary focus to isolate novel transcription factors that bind at the Clk locus to regulate expression in different oscillator neuron subgroups.

    Analysis of the Drosophila Clock promoter reveals heterogeneity in expression between subgroups of central oscillator cells and identifies a novel enhancer region.
    Gummadova JO, Coutts GA, Glossop NR.

    01/21/2010
    Sequential phosphorylation and subcellular distribution regulate the activity of the CLK protein.

    Sequential and compartment-specific phosphorylation controls the life cycle of the circadian CLOCK protein.
    Hung HC, Maurer C, Zorn D, Chang WL, Weber F., Free PMC Article

    01/21/2010
    the post-translational processing of the circadian CLOCK protein by Cytoplasmic interaction with CYCLE protein

    Cytoplasmic interaction with CYCLE promotes the post-translational processing of the circadian CLOCK protein.
    Maurer C, Hung HC, Weber F.

    01/21/2010
    DBT plays a novel noncatalytic role in recruiting additional kinases that phosphorylate CLK, thereby repressing transcription

    DOUBLETIME plays a noncatalytic role to mediate CLOCK phosphorylation and repress CLOCK-dependent transcription within the Drosophila circadian clock.
    Yu W, Zheng H, Price JL, Hardin PE., Free PMC Article

    01/21/2010
    These results define the temporal and spatial coordinates of factors that initiate Clk expression, imply that circadian photoreceptors are not activated until the end of embryogenesis.

    CLOCK expression identifies developing circadian oscillator neurons in the brains of Drosophila embryos.
    Houl JH, Ng F, Taylor P, Hardin PE., Free PMC Article

    01/21/2010
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