ZFIN ID: ZDB-PUB-161224-9
The tumor-associated YB-1 protein: new player in the circadian control of cell proliferation
Pagano, C., di Martino, O., Ruggiero, G., Guarino, A.M., Mueller, N., Siauciunaite, R., Reischl, M., Foulkes, N.S., Vallone, D., CalabrĂ², V.
Date: 2017
Source: Oncotarget   8(4): 6193-6205 (Journal)
Registered Authors: Foulkes, Nicholas-Simon, Pagano, Cristina, Vallone, Daniela
Keywords: SUMOylation, Y-box binding protein, cell cycle, cell proliferation, circadian clock
MeSH Terms:
  • Animals
  • Binding Sites
  • Cell Cycle*
  • Cell Proliferation*
  • Circadian Rhythm*
  • Cyclin A2/genetics
  • Cyclin A2/metabolism
  • DNA-Binding Proteins/genetics
  • DNA-Binding Proteins/metabolism*
  • Female
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Male
  • Promoter Regions, Genetic
  • RNA Interference
  • Signal Transduction
  • Sumoylation
  • Time Factors
  • Transfection
  • Y-Box-Binding Protein 1/genetics
  • Y-Box-Binding Protein 1/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
PubMed: 28008157 Full text @ Oncotarget
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.