Developmentally regulated GTP-binding protein 1 (DRG1)

DRG1 is a highly conserved member of the TRAFAC class of GTPases, involved in essential cellular functions. Structurally, it contains a canonical GTP-binding domain (G-domain) with five motifs (G1-G5), an N-terminal HTH domain, an insertion domain (S5D2L), and a C-terminal TGS domain. DRG1 demonstrates intrinsic potassium-dependent GTPase activity, which is stimulated by its binding partner DFRP1—this interaction protects DRG1 from ubiquitin-mediated degradation. Uniquely, DRG1 promotes microtubule polymerization and stability, required for mitotic spindle assembly, and does so independently of its GTPase activity. It also binds ribosomes, playing a role in translation regulation and in resolving stalled ribosomes, which is vital for protein synthesis. Aberrant expression of DRG1 is linked to uncontrolled proliferation and cancer, and mutations can cause developmental and neurological diseases. Small molecule inhibitors like diazaborine can block DRG1's ATPase function, offering a potential therapeutic strategy. Because DRG1 is integral to several fundamental cellular pathways, it raises challenges for targeted therapy due to risks of affecting healthy dividing cells.

Other names

NEDD3DRG-1Neural precursor cell expressed developmentally down-regulated protein 3Translation factor GTPase DRG1TANALSTRAFAC GTPase DRG1Developmentally regulated GTP binding protein 1Rbg1 (yeast ortholog)DFRP1-binding GTPase

ATPase inhibitors (e.g., diazaborine covalently modifies DRG1's ATPase domains, locking it in a nonproductive state and inhibiting ribosome assembly and protein synthesis)