G0S2 inhibits the proliferation of K562 cells by interacting with nucleolin in the cytosol

Leuk Res. 2014 Feb;38(2):210-7. doi: 10.1016/j.leukres.2013.10.006. Epub 2013 Oct 14.

Abstract

G0/G1 switch gene 2 (G0S2) is a basic protein with ill-defined function that inhibits the proliferation of hematopoietic stem cells. Herein, we show that treatment of K562 cells with 5-azacytidine (5-Aza) resulted in a 24-fold increase in G0S2 expression and a reduction in cell growth. Conversely, gene demethylation in the presence of G0S2-specific shRNA restored proliferation, further supporting an inhibitory role for G0S2 in cell proliferation. Elevated levels of G0S2 inhibited the division of K562 cells by sequestering the nucleolar phosphoprotein nucleolin in the cytosol. G0S2 inhibited the proliferation of leukemia cells in vivo in xenograft models. Collectively, our data identify a new mechanism that controls proliferation in K562 cells, suggesting a possible tumor suppressor function in leukemia cells.

Keywords: G0S2; K562; Nucleolin; Proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / antagonists & inhibitors
  • Cell Cycle Proteins / physiology*
  • Cell Proliferation* / drug effects
  • Cells, Cultured
  • Cytosol / metabolism*
  • Genes, Tumor Suppressor / physiology
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Mice
  • Mice, Nude
  • Nucleolin
  • Phosphoproteins / metabolism*
  • Protein Binding / drug effects
  • RNA, Small Interfering / pharmacology
  • RNA-Binding Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • G0S2 protein, human
  • Phosphoproteins
  • RNA, Small Interfering
  • RNA-Binding Proteins