Geranylgeranyl Transferase Type I

Geranylgeranyl transferase type I (GGTase-I) is an essential eukaryotic enzyme that catalyzes the post-translational modification of proteins through the addition of a 20-carbon geranylgeranyl isoprenoid group to specific target proteins. This process, known as geranylgeranylation, typically targets proteins with a C-terminal CaaX motif and is critical for their membrane localization and function. Substrates include over 100 proteins, notably many small GTP-binding regulatory proteins such as Rho family GTPases (e.g., RAC1, CDC42, RHOA), which are involved in cell signaling and cytoskeletal organization. GGTase-I consists of two subunits: alpha (α) and beta (β), encoded by FNTA and PGGT1B genes respectively. Because many prenylated proteins contribute to tumorigenesis or metastasis—particularly Rho family members—inhibiting GGTase-I has been explored as an anti-cancer strategy. Several inhibitors are under development targeting this pathway.

Inhibition of geranylgeranylation