Geranylgeranylated RhoB is sufficient to mediate tissue-specific suppression of Akt kinase activity by farnesyltransferase inhibitors.
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.
Liu
A
A
The Wistar Institute, Philadelphia, PA 19104, USA.
Prendergast
G C
GC
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D019556:COS Cells; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004794:Enzyme Repression / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D051231:Farnesyltranstransferase; D011905:Genes, ras; D006801:Humans; D051058:Oncogene Protein v-akt; D009928:Organ Specificity; D017368:Protein Prenylation / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis / Q000502:physiology; D015682:Retroviridae Proteins, Oncogenic / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020743:rhoB GTP-Binding Protein / Q000378:metabolism* / Q000502:physiology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D015682:Retroviridae Proteins, Oncogenic; D004815:Epidermal Growth Factor; D019883:Alkyl and Aryl Transferases; C083291:geranylgeranyltransferase type-I; D051231:Farnesyltranstransferase; D011505:Protein-Tyrosine Kinases; D051058:Oncogene Protein v-akt; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras); D020743:rhoB GTP-Binding Protein