farnèsyltransferase

Farnesyltransferase refers to a class of enzymes that catalyze the transfer of a farnesyl group, a 15-carbon isoprenoid, from a farnesyl pyrophosphate donor molecule to a protein substrate. This process, known as farnesylation, is a type of prenylation. Farnesyltransferase enzymes are crucial for the post-translational modification of proteins, influencing their localization, function, and stability.

In eukaryotes, the most well-characterized farnesyltransferases are those involved in the modification of Ras GTPases. These enzymes typically recognize a C-terminal motif on their target proteins. The farnesyl group, being lipophilic, helps to anchor the modified protein to cellular membranes, particularly the plasma membrane. This membrane association is often essential for the proper functioning of signaling proteins like Ras, which play critical roles in cell growth, differentiation, and survival.

The study of farnesyltransferases gained significant attention due to their involvement in cancer. Inhibitors of farnesyltransferase, known as farnesyltransferase inhibitors (FTIs), were developed as potential anti-cancer drugs. The rationale was that inhibiting farnesylation of oncogenic proteins like Ras would disrupt their signaling pathways and impede tumor growth. While FTIs showed promise in preclinical studies, their clinical efficacy as single agents has been limited. However, they continue to be investigated in combination therapies. Farnesyltransferase activity is also implicated in other cellular processes and diseases, making it an ongoing area of biochemical and pharmacological research.