Protein farnesyltransferase subunit alpha (FNTA) (FNTA)

Protein farnesyltransferase subunit alpha (FNTA) is the shared alpha subunit of two essential prenyltransferase enzymes: protein farnesyltransferase (FTase) and protein geranylgeranyltransferase type I (GGTase-I) [1.2.1, 1.2.2]. FTase is responsible for the post-translational farnesylation of proteins containing a C-terminal CaaX motif, a process that involves the covalent attachment of a 15-carbon farnesyl group to a cysteine residue [1.1.1, 1.5.2]. This modification is crucial for the membrane anchoring and functional activation of various signaling proteins, most notably the Ras superfamily of small GTPases and nuclear lamins [1.1.1, 1.5.1]. FNTA has emerged as a key therapeutic target because farnesylation is required for the oncogenic activity of Ras proteins and the pathogenicity of progerin in Hutchinson-Gilford Progeria Syndrome (HGPS) [1.3.1, 1.5.3]. Farnesyltransferase inhibitors (FTIs), such as lonafarnib and tipifarnib, were developed to disrupt these pathways [1.3.1, 1.3.3]. Lonafarnib is currently the only FDA-approved treatment for HGPS, effectively reducing the accumulation of toxic farnesylated progerin [1.5.3]. In oncology, while FTIs have shown limited success against KRAS-driven cancers due to compensatory geranylgeranylation, they remain a focus for HRAS-mutant malignancies and other farnesylation-dependent conditions [1.3.2, 1.4.3].

Other names

FTase-alphaCAAX farnesyltransferase subunit alphaRas proteins prenyltransferase subunit alphaType I protein geranyl-geranyltransferase subunit alphaGGTase-I-alphaFarnesyltransferase, CAAX box, subunit alphaProtein farnesyltransferase/geranylgeranyltransferase type-1 subunit alpha

Inhibition of protein farnesyltransferase activity, preventing the farnesylation of CaaX-motif proteins.