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The tumor-associated YB-1 protein: new player in the circadian control of cell proliferation

Pagano, Cristina; di Martino, Orsola; Ruggiero, Gennaro; Maria Guarino, Andrea; Mueller, Nathalie; Siauciunaite, Rima; Reischl, Markus; Simon Foulkes, Nicholas; Vallone, Daniela; Calabro, Viola



Abstract (englisch): 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.


Zugehörige Institution(en) am KIT Institut für Toxikologie und Genetik (ITG)
Institut für Angewandte Informatik (IAI)
Publikationstyp Zeitschriftenaufsatz
Jahr 2017
Sprache Englisch
Identifikator DOI: 10.18632/oncotarget.14051
ISSN: 1949-2553
KITopen ID: 1000064916
HGF-Programm 47.01.01; LK 01
Erschienen in OncoTarget
Band 8
Heft 4
Seiten 6193-6205
Bemerkung zur Veröffentlichung 2016 online veröffentlicht
Gefördert durch den KIT-Publikationsfonds
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