title: Control of sleep by a network of cell cycle genes.
abstract: Sleep is essential for health and cognition, but the molecular and neural mechanisms of sleep regulation are not well understood. We recently reported the identification of TARANIS (TARA) as a sleep-promoting factor that acts in a previously unknown arousal center in Drosophila. tara mutants exhibit a dose-dependent reduction in sleep amount of up to ∼60%. TARA and its mammalian homologs, the Trip-Br (Transcriptional Regulators Interacting with PHD zinc fingers and/or Bromodomains) family of proteins, are primarily known as transcriptional coregulators involved in cell cycle progression, and contain a conserved Cyclin-A (CycA) binding homology domain. We found that tara and CycA synergistically promote sleep, and CycA levels are reduced in tara mutants. Additional data demonstrated that Cyclin-dependent kinase 1 (Cdk1) antagonizes tara and CycA to promote wakefulness. Moreover, we identified a subset of CycA expressing neurons in the pars lateralis, a brain region proposed to be analogous to the mammalian hypothalamus, as an arousal center. In this Extra View article, we report further characterization of tara mutants and provide an extended discussion of our findings and future directions within the framework of a working model, in which a network of cell cycle genes, tara, CycA, and Cdk1, interact in an arousal center to regulate sleep.
authors.affiliation: a Department of Neuroscience ; the Farber Institute for Neurosciences; and Kimmel Cancer Center; Thomas Jefferson University ; Philadelphia , PA USA.|b Life and Health Sciences Research Institute (ICVS); School of Health Sciences; University of Minho ; 4710-057 Braga , Portugal.|c ICVS/3B's; PT Government Associate Laboratory ; 4710-057 Braga/Guimarães ; Portugal.
authors.forename: Dinis J S
authors.initials: DJ
authors.lastname: Afonso
authors.affiliation: a Department of Neuroscience ; the Farber Institute for Neurosciences; and Kimmel Cancer Center; Thomas Jefferson University ; Philadelphia , PA USA.|b Life and Health Sciences Research Institute (ICVS); School of Health Sciences; University of Minho ; 4710-057 Braga , Portugal.|c ICVS/3B's; PT Government Associate Laboratory ; 4710-057 Braga/Guimarães ; Portugal.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Machado
authors.affiliation: a Department of Neuroscience ; the Farber Institute for Neurosciences; and Kimmel Cancer Center; Thomas Jefferson University ; Philadelphia , PA USA.
authors.forename: Kyunghee
authors.initials: K
authors.lastname: Koh
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001683:Biological Clocks; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D005260:Female; D008297:Male; D009474:Neurons / Q000378:metabolism; D012890:Sleep
chemical_list: D018797:Cell Cycle Proteins; D019925:Cyclin A; D029721:Drosophila Proteins; C454818:tara protein, Drosophila; D016203:CDC2 Protein Kinase; C000601753:Cdk1 protein, Drosophila
keywords: Cdk1; CycA; Drosophila; TARANIS; behavior; cell cycle genes; pars lateralis; sleep