Failure to farnesylate Rheb protein contributes to the enrichment of G0/G1 phase cells in the Schizosaccharomyces pombe farnesyltransferase mutant

Mol Microbiol. 2001 Sep;41(6):1339-47. doi: 10.1046/j.1365-2958.2001.02599.x.


Protein farnesylation is important for a number of physiological processes, including proliferation and cell morphology. The Schizosaccharomyces pombe mutant, cpp1-, defective in farnesylation, exhibits distinct phenotypes, including morphological changes and sensitivity to the arginine analogue, canavanine. In this work, we report a novel phenotype of this mutant, enrichment of G0/G1 phase cells. This phenotype results mainly from the inability to farnesylate the Rheb G-protein, as normal cell cycle progression can be restored to the mutant by expressing a mutant form of SpRheb (SpRheb-CVIL) that can bypass farnesylation. In contrast, a farnesylation-defective mutant of SpRheb (SpRheb-SVIA) is incapable of restoring the normal cell cycle profile to the cpp1- mutant. Inhibition of SpRheb expression leads to the accumulation of cells at the G0/G1 phase of the cell cycle. This growth arrest phenotype of the sprheb- disruption can be complemented by the introduction of wild-type sprheb+. The complementation is dependent on farnesylation, as the farnesylation-defective SpRheb-SVIA mutant is incapable of complementing the sprheb- disruption. Other mutants of SpRheb, E40K and S20N, are also incapable of complementing the sprheb- disruption. Furthermore, efficient complementation can be obtained by the expression of human Rheb but not Saccharomyces cerevisiae Rheb. Our findings suggest that protein farnesylation is important for cell cycle progression of S. pombe cells and that farnesylated SpRheb is critical in this process.

Publication types

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

MeSH terms

  • Alkyl and Aryl Transferases / genetics*
  • Alkyl and Aryl Transferases / metabolism*
  • Farnesyltranstransferase
  • Fungal Proteins / metabolism*
  • G1 Phase
  • Genes, Fungal
  • Genetic Complementation Test
  • Humans
  • Monomeric GTP-Binding Proteins / metabolism*
  • Mutation
  • Neuropeptides / metabolism*
  • Phenotype
  • Protein Prenylation
  • Ras Homolog Enriched in Brain Protein
  • Resting Phase, Cell Cycle
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Schizosaccharomyces / cytology
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism*


  • Fungal Proteins
  • Neuropeptides
  • RHEB protein, human
  • Ras Homolog Enriched in Brain Protein
  • Alkyl and Aryl Transferases
  • Farnesyltranstransferase
  • Monomeric GTP-Binding Proteins