Disabled homolog 2-interacting protein (DAB2IP)

Disabled homolog 2-interacting protein (DAB2IP) is a cytoplasmic Ras GTPase-activating protein (GAP) that acts as a tumor suppressor by negatively regulating oncogenic pathways such as Ras-ERK, PI3K/AKT, TNFα/NF-κB, and WNT/β-catenin. It functions both as an enzymatic GAP for Ras and as a multi-domain adaptor/scaffold protein controlling key signaling complexes involved in cell proliferation, apoptosis, mitosis, and cellular differentiation[1][2][3][4][6][8][9]. DAB2IP loss, often by epigenetic silencing or mutation, drives tumor progression, metastasis, chromosomal instability, and resistance to chemo- and radiotherapy. Its expression correlates with survival, disease-free time, and sensitivity to therapy in multiple cancer types. DAB2IP is under active investigation as a biomarker and potential therapeutic target for reactivation strategies, though no direct drug therapies currently exist.

Other names

DAB2IPDisabled-2 interacting proteinAF9Q34AIP1KIAA1743DAB2 interaction proteinDAB2-interacting proteinASK-interacting protein 1ASK1-interacting protein 1DOC-2/DAB2 interactive proteinnGAP-like proteinDIP1/2

Drugs aiming to restore DAB2IP expression (reactivation by epigenetic modifiers); Indirect modulation or sensitization to chemotherapy/radiotherapy by targeting upstream pathways (e.g., Ras, PI3K, AKT, NF-κB)