Post-translational modifications regulate the ticking of the circadian clock

Getting a good night's sleep is on everyone's to-do list. So is, no doubt, staying awake during late afternoon seminars. Our internal clocks control these and many more workings of the body, and disruptions of the circadian clocks predispose individuals to depression, obesity and cancer. Mutations in kinases and phosphatases in hamsters, flies, fungi and humans highlight how our timepieces are regulated and provide clues as to how we might be able to manipulate them.

[1]  Yuhong Yang,et al.  Distinct roles for PP1 and PP2A in the Neurospora circadian clock. , 2004, Genes & development.

[2]  Kevin P. Keegan,et al.  A role for casein kinase 2α in the Drosophila circadian clock , 2002, Nature.

[3]  G. Landes,et al.  Isolation and Characterization of Human Casein Kinase Iε (CKI), a Novel Member of the CKI Gene Family (*) , 1995, The Journal of Biological Chemistry.

[4]  Feng Liu,et al.  Mechanism of Regulation of Casein Kinase I Activity by Group I Metabotropic Glutamate Receptors* , 2002, The Journal of Biological Chemistry.

[5]  Yoshiyuki Sakaki,et al.  Constitutive expression of the Period1 gene impairs behavioral and molecular circadian rhythms. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[6]  D. Virshup,et al.  Regulation of Casein Kinase I ε and Casein Kinase I δ by an in Vivo Futile Phosphorylation Cycle* , 1998, The Journal of Biological Chemistry.

[7]  Hongtao Yu,et al.  FWD1‐mediated degradation of FREQUENCY in Neurospora establishes a conserved mechanism for circadian clock regulation , 2003, The EMBO journal.

[8]  E. Wagner,et al.  The Molecular Clock Mediates Leptin-Regulated Bone Formation , 2005, Cell.

[9]  E. Nishida,et al.  Control of Intracellular Dynamics of Mammalian Period Proteins by Casein Kinase I ε (CKIε) and CKIδ in Cultured Cells , 2002, Molecular and Cellular Biology.

[10]  Christopher R. Jones,et al.  An hPer2 Phosphorylation Site Mutation in Familial Advanced Sleep Phase Syndrome , 2001, Science.

[11]  F. Jackson,et al.  A role for CK2 in the Drosophila circadian oscillator , 2003, Nature Neuroscience.

[12]  Kristina Kjærheim,et al.  Breast Cancer and Night Work among Norwegian Nurses , 2006, Cancer Causes & Control.

[13]  Ook Joon Yoo,et al.  PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[14]  R. Buijs,et al.  Cloning and characterization of rat casein kinase 1ϵ , 2000 .

[15]  Jason P. DeBruyne,et al.  A Clock Shock: Mouse CLOCK Is Not Required for Circadian Oscillator Function , 2006, Neuron.

[16]  T. Hirota,et al.  Ser-557-phosphorylated mCRY2 Is Degraded upon Synergistic Phosphorylation by Glycogen Synthase Kinase-3β* , 2005, Journal of Biological Chemistry.

[17]  U. Schibler,et al.  A Serum Shock Induces Circadian Gene Expression in Mammalian Tissue Culture Cells , 1998, Cell.

[18]  P. Hardin,et al.  PER-dependent rhythms in CLK phosphorylation and E-box binding regulate circadian transcription. , 2006, Genes & development.

[19]  K. Miyazaki,et al.  A Role for Glycogen Synthase Kinase-3β in the Mammalian Circadian Clock* , 2005, Journal of Biological Chemistry.

[20]  S. Golden,et al.  Resonating circadian clocks enhance fitness in cyanobacteria. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[21]  S. Shibata,et al.  The 5′ upstream region of mPer1 gene contains two promoters and is responsible for circadian oscillation , 2000, Current Biology.

[22]  Yi Liu,et al.  Molecular mechanism of light responses in Neurospora: from light-induced transcription to photoadaptation. , 2005, Genes & development.

[23]  M. Gillette,et al.  Protein Kinase G Type II Is Required for Night-to-Day Progression of the Mammalian Circadian Clock , 2004, Neuron.

[24]  J. Dunlap.  Proteins in the Neurospora Circadian Clockworks* , 2006, Journal of Biological Chemistry.

[25]  Paolo Sassone-Corsi,et al.  Circadian Clock Control by SUMOylation of BMAL1 , 2005, Science.

[26]  松尾 拓哉.  Control mechanism of the circadian clock for timing of cell division in vivo , 2004 .

[27]  M. W. Young,et al.  The Double-Time Protein Kinase Regulates the Subcellular Localization of the Drosophila Clock Protein Period , 2005, The Journal of Neuroscience.

[28]  A. Sehgal,et al.  A role for the proteasome in the light response of the timeless clock protein. , 1999, Science.

[29]  D. Virshup,et al.  Autoinhibition of casein kinase I epsilon (CKI epsilon) is relieved by protein phosphatases and limited proteolysis. , 1998, The Journal of biological chemistry.

[30]  D. Virshup,et al.  Casein Kinase I: From Obscurity to Center Stage , 2001, IUBMB life.

[31]  Qun He,et al.  Regulation of the Neurospora circadian clock by an RNA helicase. , 2005, Genes & development.

[32]  Yuhong Yang,et al.  CKI and CKII mediate the FREQUENCY-dependent phosphorylation of the WHITE COLLAR complex to close the Neurospora circadian negative feedback loop. , 2006, Genes & development.

[33]  I. Edery,et al.  Role for Slimb in the degradation of Drosophila Period protein phosphorylated by Doubletime , 2002, Nature.

[34]  J. Takahashi,et al.  Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau. , 2000, Science.

[35]  J. Emens,et al.  The circadian basis of winter depression. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[36]  T. Kondo,et al.  Reconstitution of Circadian Oscillation of Cyanobacterial KaiC Phosphorylation in Vitro , 2005, Science.

[37]  Masamitsu Iino,et al.  System-level identification of transcriptional circuits underlying mammalian circadian clocks , 2005, Nature Genetics.

[38]  K. Nagai,et al.  Identification of mPer1 Phosphorylation Sites Responsible for the Nuclear Entry* , 2004, Journal of Biological Chemistry.

[39]  M. W. Young,et al.  A Role for the Segment Polarity Gene shaggy/GSK-3 in the Drosophila Circadian Clock , 2001, Cell.

[40]  E. Meyer-Bernstein,et al.  Photic Signaling by Cryptochrome in the DrosophilaCircadian System , 2001, Molecular and Cellular Biology.

[41]  L. Pinna,et al.  One‐thousand‐and‐one substrates of protein kinase CK2? , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[42]  R. Allada,et al.  Casein kinase 2, circadian clocks, and the flight from mutagenic light , 2005, Molecular and Cellular Biochemistry.

[43]  J. Truman,et al.  Sequential Nuclear Accumulation of the Clock Proteins Period and Timeless in the Pacemaker Neurons of Drosophila melanogaster , 2002, The Journal of Neuroscience.

[44]  Christopher R. Jones,et al.  Familial advanced sleep-phase syndrome: A short-period circadian rhythm variant in humans , 1999, Nature Medicine.

[45]  Xiangzhong Zheng,et al.  Posttranslational Regulation of Drosophila PERIOD Protein by Protein Phosphatase 2A , 2004, Cell.

[46]  D. Virshup,et al.  Protein serine/threonine phosphatases: life, death, and sleeping. , 2005, Current opinion in cell biology.

[47]  D. Virshup,et al.  Phosphorylation and destabilization of human period I clock protein by human casein kinase Iε , 2000, Neuroreport.

[48]  J. Dunlap,et al.  Negative feedback defining a circadian clock: autoregulation of the clock gene frequency. , 1994, Science.

[49]  M. W. Young,et al.  double-time Is a Novel Drosophila Clock Gene that Regulates PERIOD Protein Accumulation , 1998, Cell.

[50]  J. Harper,et al.  SCF-mediated protein degradation and cell cycle control , 2005, Oncogene.

[51]  K. Yagita,et al.  Does mPER2 protein oscillate without its coding mRNA cycling?: post‐transcriptional regulation by cell clock , 2006, Genes to cells : devoted to molecular & cellular mechanisms.

[52]  Steven M. Reppert,et al.  Posttranslational Mechanisms Regulate the Mammalian Circadian Clock , 2001, Cell.

[53]  Toshiyuki Okano,et al.  Mitogen-activated Protein Kinase Phosphorylates and Negatively Regulates Basic Helix-Loop-Helix-PAS Transcription Factor BMAL1* , 2002, The Journal of Biological Chemistry.

[54]  E. Eide,et al.  The Circadian Regulatory Proteins BMAL1 and Cryptochromes Are Substrates of Casein Kinase Iε* , 2002, The Journal of Biological Chemistry.

[55]  P. Hardin,et al.  The Circadian Timekeeping System of Drosophila , 2005, Current Biology.

[56]  Yuhong Yang,et al.  Regulation of the Neurospora circadian clock by casein kinase II. , 2002, Genes & development.

[57]  M. Brunner,et al.  Transcriptional and post-transcriptional regulation of the circadian clock of cyanobacteria and Neurospora. , 2006, Genes & development.

[58]  P. Sassone-Corsi,et al.  Structural and functional features of transcription factors controlling the circadian clock. , 2005, Current opinion in genetics & development.

[59]  Daniel B Forger,et al.  Model based conjectures on mammalian clock controversies. , 2004, Journal of theoretical biology.

[60]  M. Bollen,et al.  Functional diversity of protein phosphatase-1, a cellular economizer and reset button. , 2004, Physiological reviews.

[61]  E. Maywood,et al.  mCRY 1 and mCRY 2 Are Essential Components of the Negative Limb of the Circadian Clock Feedback Loop to coordinated circadian outputs , 1999 .

[62]  P. Decoursey,et al.  Behavior of SCN-Lesioned Chipmunks in Natural Habitat: A Pilot Study , 1998, Journal of biological rhythms.

[63]  R J Konopka,et al.  Clock mutants of Drosophila melanogaster. , 1971, Proceedings of the National Academy of Sciences of the United States of America.

[64]  N. Kajimura,et al.  A Missense Variation in Human Casein Kinase I Epsilon Gene that Induces Functional Alteration and Shows an Inverse Association with Circadian Rhythm Sleep Disorders , 2004, Neuropsychopharmacology.

[65]  E. Y. Kim,et al.  Balance between DBT/CKIepsilon kinase and protein phosphatase activities regulate phosphorylation and stability of Drosophila CLOCK protein. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[66]  T. Nagase,et al.  Phosphorylation of clock protein PER1 regulates its circadian degradation in normal human fibroblasts. , 2004, The Biochemical journal.

[67]  Yuichi Inoue,et al.  Association of structural polymorphisms in the human period3 gene with delayed sleep phase syndrome , 2001, EMBO reports.

[68]  Jason P. DeBruyne,et al.  The Polycomb Group Protein EZH2 Is Required for Mammalian Circadian Clock Function*♦ , 2006, Journal of Biological Chemistry.

[69]  A. Sehgal,et al.  JETLAG Resets the Drosophila Circadian Clock by Promoting Light-Induced Degradation of TIMELESS , 2006, Science.

[70]  Ying Xu,et al.  Functional consequences of a CKIδ mutation causing familial advanced sleep phase syndrome , 2005, Nature.

[71]  Yuhong Yang,et al.  Phosphorylation of FREQUENCY Protein by Casein Kinase II Is Necessary for the Function of the Neurospora Circadian Clock , 2003, Molecular and Cellular Biology.

[72]  Michael W. Young,et al.  vrille, Pdp1, and dClock Form a Second Feedback Loop in the Drosophila Circadian Clock , 2003, Cell.

[73]  P. Nawathean,et al.  The doubletime and CKII kinases collaborate to potentiate Drosophila PER transcriptional repressor activity. , 2004, Molecular cell.

[74]  J. Harper,et al.  SCFβ-TRCP Controls Clock-dependent Transcription via Casein Kinase 1-dependent Degradation of the Mammalian Period-1 (Per1) Proteinm* , 2005, Journal of Biological Chemistry.

[75]  O. Khorkova,et al.  Human casein kinase Iδ phosphorylation of human circadian clock proteins period 1 and 2 , 2001, FEBS letters.

[76]  C. van Hoof,et al.  PP2A: the expected tumor suppressor. , 2005, Current opinion in genetics & development.

[77]  Greg Q. Butcher,et al.  The p42/44 Mitogen-activated Protein Kinase Pathway Couples Photic Input to Circadian Clock Entrainment* , 2002, The Journal of Biological Chemistry.

[78]  Daniel B. Forger,et al.  An opposite role for tau in circadian rhythms revealed by mathematical modeling. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[79]  Patrick Emery,et al.  A Rhythmic Ror , 2004, Neuron.

[80]  E. Eide,et al.  Nuclear Entry of the Circadian Regulator mPER1 Is Controlled by Mammalian Casein Kinase I ɛ , 2000, Molecular and Cellular Biology.

[81]  A. Sancar,et al.  Posttranslational regulation of the mammalian circadian clock by cryptochrome and protein phosphatase 5 , 2006, Proceedings of the National Academy of Sciences.

[82]  Adam Claridge‐Chang,et al.  Molecular genetics of timing in intrinsic circadian rhythm sleep disorders , 2002, Annals of medicine.

[83]  J. Dunlap,et al.  Phosphorylation of the Neurospora clock protein FREQUENCY determines its degradation rate and strongly influences the period length of the circadian clock. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[84]  Michael W Young,et al.  Regulation of Nuclear Entry of the Drosophila Clock Proteins Period and Timeless , 1996, Neuron.

[85]  H. Yost,et al.  Regulation of Casein Kinase Iϵ Activity by Wnt Signaling* , 2004, Journal of Biological Chemistry.

[86]  Michael W Young,et al.  The Drosophila Clock Gene double-time Encodes a Protein Closely Related to Human Casein Kinase Iε , 1998, Cell.

[87]  Peng Huang,et al.  The Circadian Gene Period2 Plays an Important Role in Tumor Suppression and DNA Damage Response In Vivo , 2002, Cell.

[88]  D. Virshup,et al.  Protein phosphatase 1 regulates the stability of the circadian protein PER 2 , 2006 .

[89]  Ueli Schibler,et al.  Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions , 2006, Nature Genetics.

[90]  R. Allada,et al.  In Vivo Circadian Function of Casein Kinase 2 Phosphorylation Sites in Drosophila PERIOD , 2005, The Journal of Neuroscience.

[91]  Fred W. Turek,et al.  Obesity and Metabolic Syndrome in Circadian Clock Mutant Mice , 2005, Science.

[92]  D. Virshup,et al.  Protein phosphatase 1 regulates the stability of the circadian protein PER2. , 2006, The Biochemical journal.

[93]  Daniel B. Forger,et al.  A detailed predictive model of the mammalian circadian clock , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[94]  Lei Yin,et al.  Nuclear Receptor Rev-erbα Is a Critical Lithium-Sensitive Component of the Circadian Clock , 2006, Science.

[95]  Jay C Dunlap,et al.  The Neurospora Checkpoint Kinase 2: A Regulatory Link Between the Circadian and Cell Cycles , 2006, Science.

[96]  Steven M. Reppert,et al.  Rhythmic histone acetylation underlies transcription in the mammalian circadian clock , 2003, Nature.

[97]  S. Fuchs,et al.  The many faces of β-TrCP E3 ubiquitin ligases: reflections in the magic mirror of cancer , 2004, Oncogene.

[98]  A. Sehgal,et al.  Role of Molecular Oscillations in Generating Behavioral Rhythms in Drosophila , 2001, Neuron.

[99]  S. Kay,et al.  Second messenger and Ras/MAPK signalling pathways regulate CLOCK/CYCLE‐dependent transcription , 2006, Journal of neurochemistry.

[100]  François Rouyer,et al.  The F-box protein Slimb controls the levels of clock proteins Period and Timeless , 2002, Nature.

[101]  M. W. Young,et al.  PER-TIM Interactions in Living Drosophila Cells: An Interval Timer for the Circadian Clock , 2006, Science.

[102]  Jay C Dunlap,et al.  Running a Clock Requires Quality Time Together , 2006, Science.

[103]  P. Hardin,et al.  Drosophila CLOCK Protein Is under Posttranscriptional Control and Influences Light-Induced Activity , 2002, Neuron.

[104]  Paolo Sassone-Corsi,et al.  Circadian Regulator CLOCK Is a Histone Acetyltransferase , 2006, Cell.

[105]  Peter Woolf,et al.  Control of Mammalian Circadian Rhythm by CKIε-Regulated Proteasome-Mediated PER2 Degradation , 2005, Molecular and Cellular Biology.

[106]  M. Menaker,et al.  A mutation of the circadian system in golden hamsters. , 1988, Science.

[107]  M. Brunner,et al.  A PEST‐like element in FREQUENCY determines the length of the circadian period in Neurospora crassa , 2001, The EMBO journal.

[108]  L. Miraglia,et al.  A Functional Genomics Strategy Reveals Rora as a Component of the Mammalian Circadian Clock , 2004, Neuron.

[109]  M. Brunner,et al.  Phosphorylation-dependent maturation of Neurospora circadian clock protein from a nuclear repressor toward a cytoplasmic activator. , 2006, Genes & development.

[110]  Yoshinobu Yamamoto,et al.  Role of Cyclic mPer2 Expression in the Mammalian Cellular Clock , 2005, Molecular and Cellular Biology.

[111]  Michael Brunner,et al.  Transcriptional Feedback of Neurospora Circadian Clock Gene by Phosphorylation-Dependent Inactivation of Its Transcription Factor , 2005, Cell.

[112]  J. Takahashi,et al.  Mammalian circadian biology: elucidating genome-wide levels of temporal organization. , 2004, Annual review of genomics and human genetics.