YB-1 as a cell cycle-regulated transcription factor facilitating cyclin A and cyclin B1 gene expression

J Biol Chem. 2003 Jul 25;278(30):27988-96. doi: 10.1074/jbc.M212966200. Epub 2003 Apr 14.

Abstract

Expression of the Y-box protein YB-1 is increased in proliferating normal and cancer cells, but its role in cell proliferation and cell cycle progression is unclear. We have identified a cell cycle-dependent relocalization of YB-1 from the cytoplasm to the nucleus at the G1/S phase transition and demonstrate that both the charged zipper and the cold shock domain are involved in regulating this process. Using cell lines that constitutively overexpress YB-1, we show that nuclear accumulation of YB-1 is associated with increased cyclin A and cyclin B1 mRNA and protein expression. We provide evidence that deregulated YB-1 expression is linked to adhesion-independent cell proliferation through the induction of cyclin A. Thus, we have identified YB-1 as a cell cycle stage-specific transcription factor important for cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Breast Neoplasms / metabolism
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • CCAAT-Enhancer-Binding Proteins / physiology*
  • Cell Adhesion
  • Cell Cycle
  • Cell Division
  • Cell Line
  • Cell Nucleus / metabolism
  • Cell Separation
  • Cyclin A / genetics
  • Cyclin A / metabolism*
  • Cyclin B / genetics
  • Cyclin B / metabolism*
  • Cyclin B1
  • Cytoplasm / metabolism
  • DNA-Binding Proteins*
  • Flow Cytometry
  • G1 Phase
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • HeLa Cells
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Kinetics
  • Microscopy, Fluorescence
  • Mutation
  • NFI Transcription Factors
  • Nuclear Proteins
  • Promoter Regions, Genetic
  • Protein Structure, Tertiary
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • S Phase
  • Subcellular Fractions / metabolism
  • Transcription Factors / metabolism*
  • Transfection
  • Y-Box-Binding Protein 1

Substances

  • CCAAT-Enhancer-Binding Proteins
  • CCNB1 protein, human
  • Cyclin A
  • Cyclin B
  • Cyclin B1
  • DNA-Binding Proteins
  • NFI Transcription Factors
  • Nuclear Proteins
  • RNA, Messenger
  • Transcription Factors
  • Y-Box-Binding Protein 1
  • YBX1 protein, human