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 language | English (US) |
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Pages (from-to) | 1991-1999 |
Number of pages | 9 |
Journal | Oncogene |
Volume | 13 |
Issue number | 9 |
State | Published - 1996 |
Keywords
- Cell cycle
- Farnesyltransferase
- Geranylgeranyltransferase
- Prenylation
- Ras
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research