Farnesyltransferase

Notes

original target text: Farnesyltransferase inhibitor

Farnesyltransferase is an enzyme that attaches a lipid tag, a fifteen-carbon farnesyl group, onto specific proteins so that they can anchor to cell membranes and function properly. Among its most studied substrates are RAS proteins, a family of signaling molecules that, when persistently active, drive uncontrolled cell growth in many cancers. Because RAS must be farnesylated to reach the inner surface of the cell membrane and transmit growth signals, blocking farnesyltransferase was pursued as a strategy to interrupt RAS-driven signaling in tumors. The enzyme also modifies other proteins, including lamin A, a structural protein of the cell nucleus; abnormal, permanently farnesylated lamin A (progerin) underlies a rare premature-aging disorder, making this enzyme relevant beyond oncology. Farnesyltransferase inhibitors are small molecules designed to occupy the enzyme's active site and prevent this lipid attachment. Their broad relevance lies in the possibility of restoring normal protein localization and dampening aberrant growth or structural signaling in diseases where farnesylation has gone awry, spanning certain RAS-mutant cancers and rare genetic conditions tied to defective protein processing.