Elimination of the vertebrate Escherichia coli Ras-like protein homologue leads to cell cycle arrest at G1 phase and apoptosis

Oncogene. 2003 Mar 6;22(9):1340-8. doi: 10.1038/sj.onc.1206287.

Abstract

Homologues of the Escherichia coli (E. coli) Ras-like protein (ERA), a GTP-binding protein with RNA binding activity, have recently been found in various species, including human, mouse, and Antirrhinum majus. Depletion of prokaryotic ERA blocks cell division without affecting chromosome segregation. However, the physiological function of eukaryotic ERA is largely unknown. We have performed a genetic analysis of chicken ERA (GdERA) in DT40 cells. Depletion of GdERA diminished the growth rate of the cells, accompanied by an accumulation of apoptotic cells. The analysis of cell cycle indicates that the elimination of GdERA caused arrest at G1 phase, but not at M phase, which highlights the distinct role of vertebrate ERA in the cell cycle progression compared to prokaryotic ERA. Furthermore, human ERA (HsERA) rescued the phenotype of GdERA-deficient cells, whereas a mutant of HsERA deprived of RNA-binding activity did not. These data suggest that vertebrate ERA regulates the G1 phase progression via an as yet unknown molecular mechanism, which involves RNA recognition by ERA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Division
  • Cell Line / cytology
  • Chickens / metabolism
  • Consensus Sequence
  • Doxycycline / pharmacology
  • G1 Phase / physiology*
  • GTP-Binding Proteins / deficiency
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / physiology*
  • Gene Targeting
  • Genes, Reporter
  • Luciferases / biosynthesis
  • Luciferases / genetics
  • Prokaryotic Cells / metabolism
  • Promoter Regions, Genetic / drug effects
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / physiology*
  • Recombinant Fusion Proteins / biosynthesis
  • Recombinant Fusion Proteins / genetics
  • Transfection
  • Vertebrates / metabolism
  • bcl-X Protein

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • RNA-Binding Proteins
  • Recombinant Fusion Proteins
  • bcl-X Protein
  • Luciferases
  • GTP-Binding Proteins
  • Doxycycline