DIRAS3

DIRAS3 (also known as ARHI) is an imprinted tumor suppressor protein and a member of the Ras superfamily of small GTPases. Unlike oncogenic Ras isoforms, DIRAS3 functions as a potent inhibitor of RAS-driven oncogenesis. It acts as a pan-RAS inhibitor by directly binding to RAS proteins (including KRAS, HRAS, and NRAS), disrupting their dimerization and nanoclustering at the plasma membrane, which effectively blocks the activation of downstream effectors such as the RAF-MEK-ERK signaling pathway. Additionally, DIRAS3 induces autophagy through the modulation of the LKB1-AMPK-ULK1 axis. Research primarily conducted at The University of Texas MD Anderson Cancer Center has demonstrated that re-expression of DIRAS3 inhibits growth in KRAS-mutant pancreatic ductal adenocarcinoma (PDAC) and low-grade serous ovarian cancer (LGSOC) cells, and sensitizes them to autophagy inhibition.

Other names

DIRAS family GTPase 3Aplasia Ras homolog member IRas-related inhibitor cell growth