title: The tumor-associated YB-1 protein: new player in the circadian control of cell proliferation.
abstract: Correct spatial and temporal control of cell proliferation is of fundamental importance for tissue homeostasis. Its deregulation has been associated with several pathological conditions. In common with almost every aspect of plant and animal biology, cell proliferation is dominated by day-night rhythms generated by the circadian clock. However, our understanding of the crosstalk between the core clock and cell cycle control mechanisms remains incomplete. In this study, using zebrafish as a vertebrate model system, we show that the nuclear localization of the Y-box binding protein 1 (YB-1), a regulator of cyclin expression and a hallmark of certain cancers, is robustly regulated by the circadian clock. We implicate clock-controlled changes in YB-1 SUMOylation as one of the mechanisms regulating its periodic nuclear entry at the beginning of the light phase. Furthermore, we demonstrate that YB-1 nuclear protein is able to downregulate cyclin A2 mRNA expression in zebrafish via its direct interaction with the cyclin A2 promoter. Thus, by acting as a direct target of cyclic posttranslational regulatory mechanisms, YB-1 serves as one bridge between the circadian clock and its cell cycle control.
authors.affiliation: Institute of Toxicology and Genetics (ITG) Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Pagano
authors.affiliation: Department of Biology, University of Naples "Federico II", 80126 Naples, Italy.
authors.forename: Orsola
authors.initials: O
authors.lastname: di Martino
authors.affiliation: Institute of Toxicology and Genetics (ITG) Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Gennaro
authors.initials: G
authors.lastname: Ruggiero
authors.affiliation: Department of Biology, University of Naples "Federico II", 80126 Naples, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Maria Guarino
authors.affiliation: Institute of Toxicology and Genetics (ITG) Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mueller
authors.affiliation: Institute of Toxicology and Genetics (ITG) Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Rima
authors.initials: R
authors.lastname: Siauciunaite
authors.affiliation: Institute for Applied Computer Science (IAI) Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Reischl
authors.affiliation: Institute of Toxicology and Genetics (ITG) Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Simon Foulkes
authors.affiliation: Institute of Toxicology and Genetics (ITG) Karlsruhe Institute of Technology, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Vallone
authors.affiliation: Department of Biology, University of Naples "Federico II", 80126 Naples, Italy.
authors.forename: Viola
authors.initials: V
authors.lastname: Calabrò
mesh_terms: D000818:Animals; D001665:Binding Sites; D002453:Cell Cycle; D049109:Cell Proliferation; D002940:Circadian Rhythm; D056751:Cyclin A2 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015398:Signal Transduction; D058207:Sumoylation; D013997:Time Factors; D014162:Transfection; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins
chemical_list: D056751:Cyclin A2; D004268:DNA-Binding Proteins; D051840:Y-Box-Binding Protein 1; D029961:Zebrafish Proteins; C541354:clocka protein, zebrafish
keywords: SUMOylation; Y-box binding protein; cell cycle; cell proliferation; circadian clock