Prenylation inhibitors in renal disease.
Members of the superfamily of Ras GTPase signalling proteins (monomeric G proteins) require post-translational carboxy-terminal prenylation to function. Prenylation is the covalent attachment of a hydrophobic prenyl group (either farnesyl or geranylgeranyl), which localises the GTPase to cell membranes. Ras proteins exert substantial control on cell proliferation and gene-transcription events, and prenylation inhibitors are now included in clinical trials for cancer. Many renal diseases are highly proliferative and are driven by a range of profibrotic cytokines. We hypothesise that inhibition of prenylation could be of substantial therapeutic benefit in such diseases, providing greater selectivity against abnormal cytokine-driven proliferation and fibrogenesis than current treatments available to nephrologists.
Khwaja
A
A
Department of Renal Medicine, Guy's, King's, and St Thomas' School of Medicine, King's College London, UK.
O'Connolly
J
J
Hendry
B M
BM
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000188:drug therapy*; D017368:Protein Prenylation / Q000187:drug effects*; D018631:ras Proteins / Q000627:therapeutic use*
D020558:GTP Phosphohydrolases; D018631:ras Proteins