Prenylation

[1] Farnesylation is a type of prenylation, a post-translational modification of proteins by which an isoprenyl group is added to a cysteine residue.

[4] The second motif for prenylation is CXC, which, in the Ras-related protein Rab3A, leads to geranylgeranylation on both cysteine residues and methyl esterification.

[4] The third motif, CC, is also found in Rab proteins, where it appears to direct only geranylgeranylation but not carboxyl methylation.

C is the cysteine that is prenylated, a is any aliphatic amino acid, and the identity of X determines which enzyme acts on the protein.

REP, therefore, plays an important role in binding and solubilising the geranylgeranyl groups and delivers the Rab protein to the relevant cell membrane.

[5] In accordance with this, farnesol and geranylgeraniol have been shown to be able to rescue effects caused by statins or nitrogenous bisphosphonates, further supporting that alcohols can be involved in prenylation, likely via phosphorylation to the corresponding isoprenoid pyrophosphate.

Proteins that undergo prenylation include Ras, which plays a central role in the development of cancer.

[7] The functional consequence of these post-translational modifications have been shown to play a role in regulating the light-dependent phosphorylation of rhodopsin, a mechanism involved in light adaptation.

[11] A 2012 study found that statin treatment increases lifespan and improves cardiac health in Drosophila by decreasing specific protein prenylation.

The study concluded, "These data are the most direct evidence to date that decreased protein prenylation can increase cardiac health and lifespan in any metazoan species, and may explain the pleiotropic (non-cholesterol related) health effects of statins.

"[12] A 2012 clinical trial explored the approach of inhibiting protein prenylation with some degree of success in the treatment of Hutchinson–Gilford progeria syndrome, a multisystem disorder which causes failure to thrive and accelerated atherosclerosis leading to early death.

Skeletal formula of the prenyl group.