Protein farnesyltransferase in embryogenesis, adult homeostasis, and tumor development

Cancer Cell. 2005 Apr;7(4):313-24. doi: 10.1016/j.ccr.2005.03.004.

Abstract

Protein farnesyltransferase (FTase) is an enzyme responsible for posttranslational modification of proteins carrying a carboxy-terminal CaaX motif. Farnesylation allows substrates to interact with membranes and protein targets. Using gene-targeted mice, we report that FTase is essential for embryonic development, but dispensable for adult homeostasis. Six-month-old FTase-deficient mice display delayed wound healing and maturation defects in erythroid cells. Embryonic fibroblasts lacking FTase have a flat morphology and reduced motility and proliferation rates. Ablation of FTase in two ras oncogene-dependent tumor models has no significant consequences for tumor initiation. However, elimination of FTase during tumor progression had a limited but significant inhibitory effect. These results should help to better understand the role of protein farnesylation in normal tissues and in tumor development.

Publication types

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

MeSH terms

  • Alkyl and Aryl Transferases / genetics
  • Alkyl and Aryl Transferases / metabolism
  • Alkyl and Aryl Transferases / physiology*
  • Animals
  • Cell Proliferation
  • Embryo Loss / genetics
  • Embryo Loss / pathology
  • Embryo, Mammalian / metabolism
  • Embryo, Mammalian / pathology
  • Embryonic Development / genetics
  • Embryonic Development / physiology*
  • Erythroid Cells / enzymology
  • Erythroid Cells / pathology
  • Estrogen Antagonists / pharmacology
  • Fibroblasts / enzymology
  • Fibroblasts / pathology
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Homeostasis / physiology*
  • Integrases / genetics
  • Liver / enzymology
  • Liver / pathology
  • Lung / enzymology
  • Lung / pathology
  • Mice
  • Mice, Knockout
  • Mutation / genetics
  • Neoplasms / enzymology*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Skin Neoplasms / enzymology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / pathology
  • Spleen / pathology
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / pharmacology
  • Wound Healing / genetics
  • Wound Healing / physiology
  • ras Proteins / genetics
  • ras Proteins / metabolism

Substances

  • Estrogen Antagonists
  • Tamoxifen
  • afimoxifene
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase
  • Cre recombinase
  • Integrases
  • ras Proteins