Geranylgeranylated RhoB is sufficient to mediate tissue-specific suppression of Akt kinase activity by farnesyltransferase inhibitors

FEBS Lett. 2000 Sep 22;481(3):205-8. doi: 10.1016/s0014-5793(00)02003-2.

Abstract

Farnesyltransferase inhibitors (FTIs) induce apoptosis by elevating the levels of geranylgeranylated RhoB (RhoB-GG) in cells. However, the mechanism by which RhoB-GG acts is unclear. Here we report that RhoB-GG is sufficient to mediate the suppressive effects of FTIs on the activity of the survival kinase Akt-1 in epithelial cells. This mechanism is tissue-specific insofar as it does not operate in fibroblasts. We discuss how the cell survival functions of RhoB and Akt may be linked biochemically in certain cell types.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • COS Cells
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Repression / drug effects
  • Epidermal Growth Factor / pharmacology
  • Farnesyltranstransferase
  • Genes, ras
  • Humans
  • Oncogene Protein v-akt
  • Organ Specificity
  • Protein Prenylation / drug effects*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / biosynthesis
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins p21(ras) / biosynthesis
  • Proto-Oncogene Proteins p21(ras) / physiology
  • Retroviridae Proteins, Oncogenic / antagonists & inhibitors*
  • Retroviridae Proteins, Oncogenic / biosynthesis
  • Retroviridae Proteins, Oncogenic / metabolism
  • Tumor Cells, Cultured
  • rhoB GTP-Binding Protein / metabolism*
  • rhoB GTP-Binding Protein / physiology

Substances

  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Retroviridae Proteins, Oncogenic
  • Epidermal Growth Factor
  • Alkyl and Aryl Transferases
  • geranylgeranyltransferase type-I
  • Farnesyltranstransferase
  • Protein-Tyrosine Kinases
  • Oncogene Protein v-akt
  • HRAS protein, human
  • Proto-Oncogene Proteins p21(ras)
  • rhoB GTP-Binding Protein