GGTase I

GGTase I catalyzes CaaX protein geranylgeranylation, a lipid posttranslational modification required by many proteins controlling growth, differentiation, morphology, cytoskeletal organization, and vesicle trafficking^[1]. Mechanistically, it modifies substrates including Rho, Rac, Cdc42, Rap1, and G-protein γ subunits, thereby supporting membrane association and small-GTPase signaling^[2][3]. In cancer-relevant models, GGTase I inhibitors disrupted oncogenic survival pathways, inhibited anchorage-dependent and anchorage-independent growth, and induced apoptosis through functionally distinct effects on RalA and RalB^[4]. In human pancreatic carcinoma cells, GGTI-298 induced p21^WAF1/CIP1^ transcription through Sp1-related promoter activity and by preventing RhoA from repressing p21 induction^[5]. Compared with FTase and RabGGTase, GGTase I belongs to the CaaX prenyltransferases, whereas Rab GTPases require REP and Rab geranylgeranyl transferase machinery^[1][6]. For experimental applications, GGTI-298, GGTI-2417, and GGTI-2147 serve as tools to test geranylgeranylation-dependent localization, signaling, growth, apoptosis, and prenylation defects^[4][5][7].