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

Andreas Vogt, Yimin Qian, Terence F. McGuire, Andrew 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 - 1996

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Protein Prenylation
Prenylation
Phase Transition
S Phase
Lovastatin
Fibroblasts
Mevalonic Acid
Farnesol
Farnesyltranstransferase
Cell Cycle Proteins
Thymidine
Cell Cycle
Flow Cytometry
Proteins
GGTI 298
FTI 277

Keywords

  • Cell cycle
  • Farnesyltransferase
  • Geranylgeranyltransferase
  • Prenylation
  • Ras

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Protein geranylgeranylation, not farnesylation, is required for the G1 to S phase transition in mouse fibroblasts. / Vogt, Andreas; Qian, Yimin; McGuire, Terence F.; Hamilton, Andrew; Sebti, Saïd M.

In: Oncogene, Vol. 13, No. 9, 1996, p. 1991-1999.

Research output: Contribution to journalArticle

Vogt, Andreas ; Qian, Yimin ; McGuire, Terence F. ; Hamilton, Andrew ; Sebti, Saïd M. / Protein geranylgeranylation, not farnesylation, is required for the G1 to S phase transition in mouse fibroblasts. In: Oncogene. 1996 ; Vol. 13, No. 9. pp. 1991-1999.
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