title: Noncanonical FK506-binding protein BDBT binds DBT to enhance its circadian function and forms foci at night.
abstract: The kinase DOUBLETIME is a master regulator of the Drosophila circadian clock, yet the mechanisms regulating its activity remain unclear. A proteomic analysis of DOUBLETIME interactors led to the identification of an unstudied protein designated CG17282. RNAi-mediated knockdown of CG17282 produced behavioral arrhythmicity and long periods and high levels of hypophosphorylated nuclear PERIOD and phosphorylated DOUBLETIME. Overexpression of DOUBLETIME in flies suppresses these phenotypes and overexpression of CG17282 in S2 cells enhances DOUBLETIME-dependent PERIOD degradation, indicating that CG17282 stimulates DOUBLETIME's circadian function. In photoreceptors, CG17282 accumulates rhythmically in PERIOD- and DOUBLETIME-dependent cytosolic foci. Finally, structural analyses demonstrated CG17282 is a noncanonical FK506-binding protein with an inactive peptide prolyl-isomerase domain that binds DOUBLETIME and tetratricopeptide repeats that may promote assembly of larger protein complexes. We have named CG17282 BRIDE OF DOUBLETIME and established it as a mediator of DOUBLETIME's effects on PERIOD, most likely in cytosolic foci that regulate PERIOD nuclear accumulation.
authors.affiliation: Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO 64110, USA.
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Fan
authors.forename: Boadi
authors.initials: B
authors.lastname: Agyekum
authors.forename: Anandakrishnan
authors.initials: A
authors.lastname: Venkatesan
authors.forename: David R
authors.initials: DR
authors.lastname: Hall
authors.forename: Andrew
authors.initials: A
authors.lastname: Keightley
authors.forename: Edward S
authors.initials: ES
authors.lastname: Bjes
authors.forename: Samuel
authors.initials: S
authors.lastname: Bouyain
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Price
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D048149:Casein Kinase 1 epsilon / Q000378:metabolism*; D002384:Catalysis; D002940:Circadian Rhythm / Q000187:drug effects; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D013058:Mass Spectrometry; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation; D020419:Photoreceptor Cells, Vertebrate / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000502:physiology; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D016559:Tacrolimus / Q000494:pharmacology*; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*
chemical_list: C000607166:BDBT protein, Drosophila; D029721:Drosophila Proteins; D007166:Immunosuppressive Agents; C113519:dco protein, Drosophila; D048149:Casein Kinase 1 epsilon; D022021:Tacrolimus Binding Proteins; D016559:Tacrolimus