Protein geranylgeranylation, not farnesylation, is required for the G1 to S phase transition in mouse fibroblasts

Andreas Vogt, Yimin Qian, Terence F. McGuire, Andrew D. Hamilton, Saïd M. Sebti

Research output: Contribution to journalArticle

Abstract

In order to assess the relative contributions of farnesylated and/or geranylgeranylated proteins on cell cycle progression from G1 to S phase we designed potent and selective farnesyltransferase (FTI-277) and geranylgeranyltransferase-I (GGTI-298) inhibitors. Flow cytometry studies showed that treatment of NIH3T3 cells with GGTI-298 or lovastatin, which inhibits both protein farnesylation and geranylgeranylation, arrested cells in G0/G1 whereas cells treated with FTI-277 progressed normally through the cell cycle. [3H]thymidine incorporation studies showed that mevalonate and geranylgeraniol, but not farnesol, released the lovastatin G1 block. Furthermore, mevalonate release of the lovastatin G1 block was inhibited by GGTI-298 but not by FTI-277. These results demonstrate that geranylgeranylated proteins are required for cells to proceed from G1 to S phase, and that farnesylated proteins do not play an essential role in the G1 to S phase transition.

Original languageEnglish (US)
Pages (from-to)1991-1999
Number of pages9
JournalOncogene
Volume13
Issue number9
StatePublished - Dec 9 1996

    Fingerprint

Keywords

  • Cell cycle
  • Farnesyltransferase
  • Geranylgeranyltransferase
  • Prenylation
  • Ras

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this