The circadian molecular clock regulates and coordinates cellular metabolism with the organism's daily feeding and fasting cycle. Disruption of circadian rhythm, such as through jet lag or shift work, appears to heighten cancer risk in humans and accelerates tumorigenesis in animal models. The mammalian clock is a circuitry of transcription factors anchored by BMAL1-CLOCK, which drives diurnal oscillation of metabolic gene expression. The clock is independent of the cell cycle, but they can couple to coordinate normal cell proliferation. Expression of components of the clock, BMAL1 and PER2, appears decreased in human cancers. PER2 promotes p53 function, while BMAL1 expression is suppressed by MYC, linking key oncogenic drivers to the circadian clock. This review provides an overview of the clock, its regulation of metabolism, the connection to cancer shown in studies spanning from human epidemiology to cell biology, and the therapeutic implications of the circadian rhythm.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Aguilar-Arnal L, Sassone-Corsi P. 2013. The circadian epigenome: how metabolism talks to chromatin remodeling. Curr. Opin. Cell Biol. 25:170–76 [Google Scholar]
  2. Altman BJ. 2016. Cancer clocks out for lunch: disruption of circadian rhythm and metabolic oscillation in cancer. Front. Cell Dev. Biol. 4:62 [Google Scholar]
  3. Altman BJ, Hsieh AL, Gouw AM, Dang CV. 2017. Correspondence: oncogenic MYC persistently upregulates the molecular clock component REV-ERBα. Nat. Commun. 8:14862 [Google Scholar]
  4. Altman BJ, Hsieh AL, Sengupta A, Krishnanaiah SY, Stine ZE. et al. 2015. MYC disrupts the circadian clock and metabolism in cancer cells. Cell Metab 22:1009–19 [Google Scholar]
  5. Amati B, Alevizopoulos K, Vlach J. 1998. Myc and the cell cycle. Front. Biosci. 3:d250–68 [Google Scholar]
  6. Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C. et al. 2008. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134:317–28 [Google Scholar]
  7. Atger F, Gobet C, Marquis J, Martin E, Wang J. et al. 2015. Circadian and feeding rhythms differentially affect rhythmic mRNA transcription and translation in mouse liver. PNAS 112:E6579–88 [Google Scholar]
  8. Bass J. 2012. Circadian topology of metabolism. Nature 491:348–56 [Google Scholar]
  9. Bass J, Lazar MA. 2016. Circadian time signatures of fitness and disease. Science 354:994–99 [Google Scholar]
  10. Bass J, Takahashi JS. 2010. Circadian integration of metabolism and energetics. Science 330:1349–54 [Google Scholar]
  11. Bieler J, Cannavo R, Gustafson K, Gobet C, Gatfield D, Naef F. 2014. Robust synchronization of coupled circadian and cell cycle oscillators in single mammalian cells. Mol. Syst. Biol. 10:739 [Google Scholar]
  12. Blask DE, Dauchy RT, Dauchy EM, Mao L, Hill SM. et al. 2014. Light exposure at night disrupts host/cancer circadian regulatory dynamics: impact on the Warburg effect, lipid signaling and tumor growth prevention. PLOS ONE 9:e102776 [Google Scholar]
  13. Brandauer J, Vienberg SG, Andersen MA, Ringholm S, Risis S. et al. 2013. AMP-activated protein kinase regulates nicotinamide phosphoribosyl transferase expression in skeletal muscle. J. Physiol. 591:5207–20 [Google Scholar]
  14. Caussanel JP, Levi F, Brienza S, Misset JL, Itzhaki M. et al. 1990. Phase I trial of 5-day continuous venous infusion of oxaliplatin at circadian rhythm-modulated rate compared with constant rate. J. Natl. Cancer Inst. 82:1046–50 [Google Scholar]
  15. Chaix A, Zarrinpar A, Panda S. 2016. The circadian coordination of cell biology. J. Cell Biol. 215:15–25 [Google Scholar]
  16. Chan S, Rowbottom L, McDonald R, Bjarnason GA, Tsao M. et al. 2017. Does the time of radiotherapy affect treatment outcomes? A review of the literature. Clin. Oncol. 29:231–38 [Google Scholar]
  17. Cho H, Zhao X, Hatori M, Yu RT, Barish GD. et al. 2012. Regulation of circadian behaviour and metabolism by REV-ERB-α and REV-ERB-β. Nature 485:123–27 [Google Scholar]
  18. Cohen SE, Golden SS. 2015. Circadian rhythms in cyanobacteria. Microbiol. Mol. Biol. Rev. 79:373–85 [Google Scholar]
  19. Dang CV. 2012. MYC on the path to cancer. Cell 149:22–35 [Google Scholar]
  20. Dibner C, Schibler U, Albrecht U. 2010. The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu. Rev. Physiol. 72:517–49 [Google Scholar]
  21. Dickson I. 2017. Gut microbiota: intestinal microbiota oscillations regulate host circadian physiology. Nat. Rev. Gastroenterol. Hepatol. 14:67 [Google Scholar]
  22. Doherty JR, Yang C, Scott KE, Cameron MD, Fallahi M. et al. 2014. Blocking lactate export by inhibiting the Myc target MCT1 disables glycolysis and glutathione synthesis. Cancer Res 74:908–20 [Google Scholar]
  23. Donnelly N, Gorman AM, Gupta S, Samali A. 2013. The eIF2α kinases: their structures and functions. Cell. Mol. Life Sci. 70:3493–511 [Google Scholar]
  24. Eckel-Mahan K, Sassone-Corsi P. 2009. Metabolism control by the circadian clock and vice versa. Nat. Struct. Mol. Biol. 16:462–67 [Google Scholar]
  25. Edgar RS, Green EW, Zhao Y, van Ooijen G, Olmedo M. et al. 2012. Peroxiredoxins are conserved markers of circadian rhythms. Nature 485:459–64 [Google Scholar]
  26. El Cheikh R, Bernard S, El Khatib N. 2014. Modeling circadian clock–cell cycle interaction effects on cell population growth rates. J. Theor. Biol. 363:318–31 [Google Scholar]
  27. Ercolani L, Ferrari A, De Mei C, Parodi C, Wade M, Grimaldi B. 2015. Circadian clock: Time for novel anticancer strategies?. Pharmacol. Res. 100:288–95 [Google Scholar]
  28. Erren TC, Morfeld P, Foster RG, Reiter RJ, Gross JV, Westermann IK. 2016. Sleep and cancer: synthesis of experimental data and meta-analyses of cancer incidence among some 1,500,000 study individuals in 13 countries. Chronobiol. Int. 33:325–50 [Google Scholar]
  29. Feillet C, Krusche P, Tamanini F, Janssens RC, Downey MJ. et al. 2014. Phase locking and multiple oscillating attractors for the coupled mammalian clock and cell cycle. PNAS 111:9828–33 [Google Scholar]
  30. Filipski E, King VM, Li X, Granda TG, Mormont MC. et al. 2003. Disruption of circadian coordination accelerates malignant growth in mice. Pathologie Biologie 51:216–19 [Google Scholar]
  31. Filipski E, Li XM, Levi F. 2006. Disruption of circadian coordination and malignant growth. Cancer Causes Control 17:509–14 [Google Scholar]
  32. Fonken LK, Aubrecht TG, Melendez-Fernandez OH, Weil ZM, Nelson RJ. 2013. Dim light at night disrupts molecular circadian rhythms and increases body weight. J. Biol. Rhythms 28:262–71 [Google Scholar]
  33. Fu L, Lee CC. 2003. The circadian clock: pacemaker and tumour suppressor. Nat. Rev. Cancer 3:350–61 [Google Scholar]
  34. Fu L, Pelicano H, Liu J, Huang P, Lee C. 2002. The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell 111:41–50 [Google Scholar]
  35. Fustin JM, Doi M, Yamada H, Komatsu R, Shimba S, Okamura H. 2012. Rhythmic nucleotide synthesis in the liver: temporal segregation of metabolites. Cell Rep 1:341–49 [Google Scholar]
  36. Gerard C, Goldbeter A. 2012. Entrainment of the mammalian cell cycle by the circadian clock: modeling two coupled cellular rhythms. PLOS Comput. Biol. 8:e1002516 [Google Scholar]
  37. Gomes AL, Teijeiro A, Buren S, Tummala KS, Yilmaz M. et al. 2016. Metabolic inflammation-associated IL-17A causes non-alcoholic steatohepatitis and hepatocellular carcinoma. Cancer Cell 30:161–75 [Google Scholar]
  38. Gotoh T, Kim JK, Liu J, Vila-Caballer M, Stauffer PE. et al. 2016. Model-driven experimental approach reveals the complex regulatory distribution of p53 by the circadian factor Period 2. PNAS 113:13516–21 [Google Scholar]
  39. Gotoh T, Vila-Caballer M, Liu J, Schiffhauer S, Finkielstein CV. 2015. Association of the circadian factor Period 2 to p53 influences p53’s function in DNA-damage signaling. Mol. Biol. Cell 26:359–72 [Google Scholar]
  40. Gotoh T, Vila-Caballer M, Santos CS, Liu J, Yang J, Finkielstein CV. 2014. The circadian factor Period 2 modulates p53 stability and transcriptional activity in unstressed cells. Mol. Biol. Cell 25:3081–93 [Google Scholar]
  41. Grechez-Cassiau A, Rayet B, Guillaumond F, Teboul M, Delaunay F. 2008. The circadian clock component BMAL1 is a critical regulator of p21WAF1/CIP1 expression and hepatocyte proliferation. J. Biol. Chem. 283:4535–42 [Google Scholar]
  42. Greene MW. 2012. Circadian rhythms and tumor growth. Cancer Lett 318:115–23 [Google Scholar]
  43. Greenham K, McClung CR. 2015. Integrating circadian dynamics with physiological processes in plants. Nat. Rev. Genet. 16:598–610 [Google Scholar]
  44. Hardie DG, Schaffer BE, Brunet A. 2016. AMPK: an energy-sensing pathway with multiple inputs and outputs. Trends Cell Biol 26:190–201 [Google Scholar]
  45. Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD. et al. 2003. An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol. Cell 11:619–33 [Google Scholar]
  46. Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA. et al. 2012. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab 15:848–60 [Google Scholar]
  47. He C, Anand ST, Ebell MH, Vena JE, Robb SW. 2015. Circadian disrupting exposures and breast cancer risk: a meta-analysis. Int. Arch. Occup. Environ. Health 88:533–47 [Google Scholar]
  48. Heckman CJ, Kloss JD, Feskanich D, Culnan E, Schernhammer ES. 2017. Associations among rotating night shift work, sleep and skin cancer in Nurses' Health Study II participants. Occup. Environ. Med. 74:169–75 [Google Scholar]
  49. Hemmers S, Rudensky AY. 2015. The cell-intrinsic circadian clock is dispensable for lymphocyte differentiation and function. Cell Rep 11:1339–49 [Google Scholar]
  50. Hirano A, Braas D, Fu YH, Ptacek LJ. 2017. FAD regulates CRYPTOCHROME protein stability and circadian clock in mice. Cell Rep 19:255–66 [Google Scholar]
  51. Horiguchi M, Koyanagi S, Hamdan AM, Kakimoto K, Matsunaga N. et al. 2013. Rhythmic control of the ARF-MDM2 pathway by ATF4 underlies circadian accumulation of p53 in malignant cells. Cancer Res 73:2639–49 [Google Scholar]
  52. Huber AL, Papp SJ, Chan AB, Henriksson E, Jordan SD. et al. 2016. CRY2 and FBXL3 cooperatively degrade c-MYC. Mol. Cell 64:774–89 [Google Scholar]
  53. Hughes ME, DiTacchio L, Hayes KR, Vollmers C, Pulivarthy S. et al. 2009. Harmonics of circadian gene transcription in mammals. PLOS Genet 5:e1000442 [Google Scholar]
  54. Igarashi T, Izumi H, Uchiumi T, Nishio K, Arao T. et al. 2007. Clock and ATF4 transcription system regulates drug resistance in human cancer cell lines. Oncogene 26:4749–60 [Google Scholar]
  55. Int. Agency Res. Cancer. 2017. IARC monographs on the evaluation of carcinogenic risks to humans 1–119 Lyon, France: Int. Agency Res. Cancer. http://monographs.iarc.fr/ENG/Classification/latest_classif.php
  56. Jacobi D, Liu S, Burkewitz K, Kory N, Knudsen NH. et al. 2015. Hepatic Bmal1 regulates rhythmic mitochondrial dynamics and promotes metabolic fitness. Cell Metab 22:709–20 [Google Scholar]
  57. Jang C, Lahens NF, Hogenesch JB, Sehgal A. 2015. Ribosome profiling reveals an important role for translational control in circadian gene expression. Genome Res 25:1836–47 [Google Scholar]
  58. Janich P, Arpat AB, Castelo-Szekely V, Lopes M, Gatfield D. 2015. Ribosome profiling reveals the rhythmic liver translatome and circadian clock regulation by upstream open reading frames. Genome Res 25:1848–59 [Google Scholar]
  59. Janich P, Pascual G, Merlos-Suarez A, Batlle E, Ripperger J. et al. 2011. The circadian molecular clock creates epidermal stem cell heterogeneity. Nature 480:209–14 [Google Scholar]
  60. Jiang W, Zhao S, Jiang X, Zhang E, Hu G. et al. 2016. The circadian clock gene Bmal1 acts as a potential anti-oncogene in pancreatic cancer by activating the p53 tumor suppressor pathway. Cancer Lett 371:314–25 [Google Scholar]
  61. Johnson CH, Zhao C, Xu Y, Mori T. 2017. Timing the day: What makes bacterial clocks tick. Nat. Rev. Microbiol. 15:232–42 [Google Scholar]
  62. Jordan SD, Lamia KA. 2013. AMPK at the crossroads of circadian clocks and metabolism. Mol. Cell. Endocrinol. 366:163–69 [Google Scholar]
  63. Jouffe C, Cretenet G, Symul L, Martin E, Atger F. et al. 2013. The circadian clock coordinates ribosome biogenesis. PLOS Biol 11:e1001455 [Google Scholar]
  64. Kecklund G, Axelsson J. 2016. Health consequences of shift work and insufficient sleep. BMJ 355:i5210 [Google Scholar]
  65. Kettner NM, Voicu H, Finegold MJ, Coarfa C, Sreekumar A. et al. 2016. Circadian homeostasis of liver metabolism suppresses hepatocarcinogenesis. Cancer Cell 30:909–24 [Google Scholar]
  66. Kiessling S, Beaulieu-Laroche L, Blum ID, Landgraf D, Welsh DK. et al. 2017. Enhancing circadian clock function in cancer cells inhibits tumor growth. BMC Biol 15:13 [Google Scholar]
  67. Kondratov RV, Kondratova AA, Gorbacheva VY, Vykhovanets OV, Antoch MP. 2006. Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. Genes Dev 20:1868–73 [Google Scholar]
  68. Kowalska E, Ripperger JA, Hoegger DC, Bruegger P, Buch T. et al. 2013. NONO couples the circadian clock to the cell cycle. PNAS 110:1592–99 [Google Scholar]
  69. Koyanagi S, Hamdan AM, Horiguchi M, Kusunose N, Okamoto A. et al. 2011. cAMP-response element (CRE)-mediated transcription by activating transcription factor-4 (ATF4) is essential for circadian expression of the Period2 gene. J. Biol. Chem. 286:32416–23 [Google Scholar]
  70. Krishnaiah SY, Wu G, Altman BJ, Growe J, Rhoades SD. et al. 2017. Clock regulation of metabolites reveals coupling between transcription and metabolism. Cell Metab 25:961–74.e4 [Google Scholar]
  71. Labrecque N, Cermakian N. 2015. Circadian clocks in the immune system. J. Biol. Rhythms 30:277–90 [Google Scholar]
  72. Lamia KA, Sachdeva UM, DiTacchio L, Williams EC, Alvarez JG. et al. 2009. AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 326:437–40 [Google Scholar]
  73. Lauriola M, Enuka Y, Zeisel A, D'Uva G, Roth L. et al. 2014. Diurnal suppression of EGFR signalling by glucocorticoids and implications for tumour progression and treatment. Nat. Commun. 5:5073 [Google Scholar]
  74. Lee S, Donehower LA, Herron AJ, Moore DD, Fu L. 2010. Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice. PLOS ONE 5:e10995 [Google Scholar]
  75. Leproult R, Holmback U, Van Cauter E. 2014. Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss. Diabetes 63:1860–69 [Google Scholar]
  76. Levi F. 2001. Circadian chronotherapy for human cancers. Lancet. Oncol. 2:307–15 [Google Scholar]
  77. Li W, Liu L, Liu D, Jin S, Yang Y. et al. 2016. Decreased circadian component Bmal1 predicts tumor progression and poor prognosis in human pancreatic ductal adenocarcinoma. Biochem. Biophys. Res. Commun. 472:156–62 [Google Scholar]
  78. Lipton JO, Yuan ED, Boyle LM, Ebrahimi-Fakhari D, Kwiatkowski E. et al. 2015. The circadian protein BMAL1 regulates translation in response to S6K1-mediated phosphorylation. Cell 161:1138–51 [Google Scholar]
  79. Logan RW, Zhang C, Murugan S, O'Connell S, Levitt D. et al. 2012. Chronic shift-lag alters the circadian clock of NK cells and promotes lung cancer growth in rats. J. Immunol. 188:2583–91 [Google Scholar]
  80. Longo VD, Panda S. 2016. Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cell Metab 23:1048–59 [Google Scholar]
  81. Maillo C, Martin J, Sebastian D, Hernandez-Alvarez M, Garcia-Rocha M. et al. 2017. Circadian- and UPR-dependent control of CPEB4 mediates a translational response to counteract hepatic steatosis under ER stress. Nat. Cell Biol. 19:94–105 [Google Scholar]
  82. Masri S, Cervantes M, Sassone-Corsi P. 2013. The circadian clock and cell cycle: interconnected biological circuits. Curr. Opin. Cell Biol. 25:730–34 [Google Scholar]
  83. Matsuo T, Yamaguchi S, Mitsui S, Emi A, Shimoda F, Okamura H. 2003. Control mechanism of the circadian clock for timing of cell division in vivo. Science 302:255–59 [Google Scholar]
  84. Mauvoisin D, Wang J, Jouffe C, Martin E, Atger F. et al. 2014. Circadian clock-dependent and -independent rhythmic proteomes implement distinct diurnal functions in mouse liver. PNAS 111:167–72 [Google Scholar]
  85. McHill AW, Melanson EL, Higgins J, Connick E, Moehlman TM. et al. 2014. Impact of circadian misalignment on energy metabolism during simulated nightshift work. PNAS 111:17302–7 [Google Scholar]
  86. Mihaylova MM, Shaw RJ. 2011. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat. Cell Biol. 13:1016–23 [Google Scholar]
  87. Miki T, Matsumoto T, Zhao Z, Lee CC. 2013. p53 regulates Period2 expression and the circadian clock. Nat. Commun. 4:2444 [Google Scholar]
  88. Miller BH, McDearmon EL, Panda S, Hayes KR, Zhang J. et al. 2007. Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation. PNAS 104:3342–47 [Google Scholar]
  89. Mteyrek A, Filipski E, Guettier C, Okyar A, Levi F. 2016. Clock gene Per2 as a controller of liver carcinogenesis. Oncotarget 7:85832–47 [Google Scholar]
  90. Mukherji A, Kobiita A, Damara M, Misra N, Meziane H. et al. 2015. Shifting eating to the circadian rest phase misaligns the peripheral clocks with the master SCN clock and leads to a metabolic syndrome. PNAS 112:E6691–98 [Google Scholar]
  91. Mullenders J, Fabius AW, Madiredjo M, Bernards R, Beijersbergen RL. 2009. A large scale shRNA barcode screen identifies the circadian clock component ARNTL as putative regulator of the p53 tumor suppressor pathway. PLOS ONE 4:e4798 [Google Scholar]
  92. Muller PA, Vousden KH. 2014. Mutant p53 in cancer: new functions and therapeutic opportunities. Cancer Cell 25:304–17 [Google Scholar]
  93. Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J. et al. 2008. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134:329–40 [Google Scholar]
  94. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P. 2009. Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 324:654–57 [Google Scholar]
  95. Neufeld-Cohen A, Robles MS, Aviram R, Manella G, Adamovich Y. et al. 2016. Circadian control of oscillations in mitochondrial rate-limiting enzymes and nutrient utilization by PERIOD proteins. PNAS 113:E1673–82 [Google Scholar]
  96. O'Donnell AJ, Schneider P, McWatters HG, Reece SE. 2011. Fitness costs of disrupting circadian rhythms in malaria parasites. Proc. Biol. Sci. 278:2429–36 [Google Scholar]
  97. Ozturk N, Lee JH, Gaddameedhi S, Sancar A. 2009. Loss of cryptochrome reduces cancer risk in p53 mutant mice. PNAS 106:2841–46 [Google Scholar]
  98. Pakos-Zebrucka K, Koryga I, Mnich K, Ljujic M, Samali A, Gorman AM. 2016. The integrated stress response. EMBO Rep 17:1374–95 [Google Scholar]
  99. Panda S. 2016. Circadian physiology of metabolism. Science 354:1008–15 [Google Scholar]
  100. Panda S, Antoch MP, Miller BH, Su AI, Schook AB. et al. 2002. Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109:307–20 [Google Scholar]
  101. Papagiannakopoulos T, Bauer MR, Davidson SM, Heimann M, Subbaraj L. et al. 2016. Circadian rhythm disruption promotes lung tumorigenesis. Cell Metab 24:324–31 [Google Scholar]
  102. Paranjpe DA, Sharma VK. 2005. Evolution of temporal order in living organisms. J. Circadian Rhythms 3:7 [Google Scholar]
  103. Peek CB, Affinati AH, Ramsey KM, Kuo HY, Yu W. et al. 2013. Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342:1243417 [Google Scholar]
  104. Poole EM, Schernhammer ES, Tworoger SS. 2011. Rotating night shift work and risk of ovarian cancer. Cancer Epidemiol. Biomark. Prev. 20:934–38 [Google Scholar]
  105. Puram RV, Kowalczyk MS, de Boer CG, Schneider RK, Miller PG. et al. 2016. Core circadian clock genes regulate leukemia stem cells in AML. Cell 165:303–16 [Google Scholar]
  106. Ramsey KM, Yoshino J, Brace CS, Abrassart D, Kobayashi Y. et al. 2009. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 324:651–54 [Google Scholar]
  107. Ray S, Reddy AB. 2016. Cross-talk between circadian clocks, sleep-wake cycles, and metabolic networks: dispelling the darkness. BioEssays 38:394–405 [Google Scholar]
  108. Reddy AB, Karp NA, Maywood ES, Sage EA, Deery M. et al. 2006. Circadian orchestration of the hepatic proteome. Curr. Biol. 16:1107–15 [Google Scholar]
  109. Relogio A, Thomas P, Medina-Perez P, Reischl S, Bervoets S. et al. 2014. Ras-mediated deregulation of the circadian clock in cancer. PLOS Genet 10:e1004338 [Google Scholar]
  110. Repouskou A, Prombona A. 2016. c-MYC targets the central oscillator gene Per1 and is regulated by the circadian clock at the post-transcriptional level. Biochim. Biophys. Acta 1859:541–52 [Google Scholar]
  111. Rey G, Reddy AB. 2013. Connecting cellular metabolism to circadian clocks. Trends Cell Biol 23:234–41 [Google Scholar]
  112. Robles MS, Cox J, Mann M. 2014. In-vivo quantitative proteomics reveals a key contribution of post-transcriptional mechanisms to the circadian regulation of liver metabolism. PLOS Genet 10:e1004047 [Google Scholar]
  113. Robles MS, Humphrey SJ, Mann M. 2017. Phosphorylation is a central mechanism for circadian control of metabolism and physiology. Cell Metab 25:118–27 [Google Scholar]
  114. Saxton RA, Sabatini DM. 2017. mTOR signaling in growth, metabolism, and disease. Cell 168:960–76 [Google Scholar]
  115. Scheiermann C, Kunisaki Y, Frenette PS. 2013. Circadian control of the immune system. Nat. Rev. Immunol. 13:190–98 [Google Scholar]
  116. Sengupta A, Krishnaiah SY, Rhoades S, Growe J, Slaff B. et al. 2016. Deciphering the duality of clock and growth metabolism in a cell autonomous system using NMR profiling of the secretome. Metabolites 6:23 https://doi.org/10.3390/metabo6030023 [Crossref] [Google Scholar]
  117. Shostak A, Ruppert B, Diernfellner A, Brunner M. 2017. Correspondence: Reply to ‘Oncogenic MYC persistently upregulates the molecular clock component REV-ERBα’. Nat. Commun. 8:14918 [Google Scholar]
  118. Shostak A, Ruppert B, Ha N, Bruns P, Toprak UH. et al. 2016. MYC/MIZ1-dependent gene repression inversely coordinates the circadian clock with cell cycle and proliferation. Nat. Commun. 7:11807 [Google Scholar]
  119. Smolensky MH, Hermida RC, Reinberg A, Sackett-Lundeen L, Portaluppi F. 2016. Circadian disruption: new clinical perspective of disease pathology and basis for chronotherapeutic intervention. Chronobiol. Int. 33:1101–19 [Google Scholar]
  120. Sookoian S, Gemma C, Fernandez Gianotti T, Burgueno A, Alvarez A. et al. 2007. Effects of rotating shift work on biomarkers of metabolic syndrome and inflammation. J. Intern. Med. 261:285–92 [Google Scholar]
  121. Takahashi JS. 2017. Transcriptional architecture of the mammalian circadian clock. Nat. Rev. Genet. 18:164–79 [Google Scholar]
  122. Thaiss CA, Levy M, Korem T, Dohnalova L, Shapiro H. et al. 2016. Microbiota diurnal rhythmicity programs host transcriptome oscillations. Cell 167:1495–510.e12 [Google Scholar]
  123. Thaiss CA, Zeevi D, Levy M, Zilberman-Schapira G, Suez J. et al. 2014. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Cell 159:514–29 [Google Scholar]
  124. Traynard P, Feillet C, Soliman S, Delaunay F, Fages F. 2016. Model-based investigation of the circadian clock and cell cycle coupling in mouse embryonic fibroblasts: prediction of RevErb-α up-regulation during mitosis. Biosyst 149:59–69 [Google Scholar]
  125. Truong T, Liquet B, Menegaux F, Plancoulaine S, Laurent-Puig P. et al. 2014. Breast cancer risk, nightwork, and circadian clock gene polymorphisms. Endocr.-Relat. Cancer 21:629–38 [Google Scholar]
  126. Umemura Y, Koike N, Matsumoto T, Yoo SH, Chen Z. et al. 2014. Transcriptional program of Kpna2/Importin-α2 regulates cellular differentiation-coupled circadian clock development in mammalian cells. PNAS 111:E5039–48 [Google Scholar]
  127. Whiteman DC, Wilson LF. 2016. The fractions of cancer attributable to modifiable factors: a global review. Cancer Epidemiol 44:203–21 [Google Scholar]
  128. Woelfle MA, Ouyang Y, Phanvijhitsiri K, Johnson CH. 2004. The adaptive value of circadian clocks: an experimental assessment in cyanobacteria. Curr. Biol. 14:1481–86 [Google Scholar]
  129. Woller A, Duez H, Staels B, Lefranc M. 2016. A mathematical model of the liver circadian clock linking feeding and fasting cycles to clock function. Cell Rep 17:1087–97 [Google Scholar]
  130. Yang G, Chen L, Grant GR, Paschos G, Song WL. et al. 2016. Timing of expression of the core clock gene Bmal1 influences its effects on aging and survival. Sci. Transl. Med. 8:324ra16 [Google Scholar]
  131. Yu X, Rollins D, Ruhn KA, Stubblefield JJ, Green CB. et al. 2013. TH17 cell differentiation is regulated by the circadian clock. Science 342:727–30 [Google Scholar]
  132. Zhang R, Lahens NF, Ballance HI, Hughes ME, Hogenesch JB. 2014. A circadian gene expression atlas in mammals: implications for biology and medicine. PNAS 111:16219–24 [Google Scholar]
  133. Zienolddiny S, Haugen A, Lie JA, Kjuus H, Anmarkrud KH, Kjaerheim K. 2013. Analysis of polymorphisms in the circadian-related genes and breast cancer risk in Norwegian nurses working night shifts. Breast Cancer Res 15:R53 [Google Scholar]

Data & Media loading...

Supplementary Data

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error