GTP-binding protein Di-Ras3 (DIRAS3)

GTP-binding protein Di-Ras3 (DIRAS3) is a small GTPase of the Ras superfamily distinguished by its tumor-suppressing function, in contrast to the primarily oncogenic role of other Ras proteins[1][3]. Expressed from a maternally imprinted gene (monoallelically, paternal allele), DIRAS3 is normally present in healthy ovarian and breast epithelial cells but is frequently lost in ovarian and breast cancers, with loss driven by gene deletion or promoter hypermethylation[1][3]. DIRAS3 inhibits cell growth and proliferation through mechanisms including strong repression of the cyclin D1 promoter, induction of cell cycle inhibitor p21, inhibition of Ras/MAPK signaling, and, uniquely, induction of autophagy via direct interaction with the autophagy-initiating complex (BECN1-PIK3C3-ATG14)[2]. Re-expression of DIRAS3 in cancer cells causes cell cycle arrest, reduced motility, and induction of autophagy, contributing to both tumor suppression and the ability of cancer cells to survive in a dormant state after therapy[2]. DIRAS3 is not currently the target of any known approved drugs, and therapeutic strategies would require reactivation or demethylation rather than pharmacological inhibition. DIRAS3 loss is a potential biomarker for certain cancers and for autophagy-driven tumor dormancy[1][2][3].

Other names

DIRAS3ARHINOEY2Distinct subgroup of the Ras family member 3Rho-related GTP-binding protein RhoIras homolog gene family member Iaplysia ras homology member I