FTase 2mg vials

FTase stands for Farnesyltransferase — an enzyme that plays a key role in a type of post-translational modification called protein prenylation.

Here’s a clear breakdown of what it does and why it’s important:

1. What FTase Does

FTase catalyzes the attachment of a farnesyl group (a 15-carbon isoprenoid lipid) from farnesyl pyrophosphate (FPP) to specific proteins that have a CAAX motif at their C-terminus.

CAAX motif:

• C = cysteine
• A = aliphatic amino acid
• X = usually methionine, serine, alanine, or glutamine

This process is called farnesylation.

2. Purpose of Farnesylation

Adding a lipid (farnesyl) group:

• Anchors the protein to cell membranes (since lipids are hydrophobic)
• Allows proper localization and signaling of the protein inside the cell
• Is critical for function of several small GTP-binding proteins (e.g., Ras, Rheb, and others)

3. FTase and the HRAS Gene

FTase is particularly important because it modifies Ras proteins (HRAS, KRAS, NRAS).

• The HRAS gene encodes a protein that helps regulate cell growth and division.
• Farnesylation by FTase enables HRAS to attach to the inner surface of the cell membrane, which is essential for its signaling activity.
• When HRAS is mutated, it can become permanently active — driving uncontrolled cell division and cancer.
• FTase inhibitors (FTIs) were developed to block farnesylation of Ras, aiming to stop cancer growth.

4. Farnesyltransferase Inhibitors (FTIs)

Drugs that block FTase can:

• Prevent mutant Ras proteins from anchoring to the membrane
• Disrupt their oncogenic (cancer-promoting) signaling

Examples:

• Tipifarnib
• Lonafarnib (also used in progeria treatment)
• BMS-214662

These have been explored in cancers such as acute myeloid leukemia, pancreatic, and lung cancer.

Summary