Disabled homolog 2-interacting protein (DAB2IP) (DAB2IP)

Disabled homolog 2-interacting protein (DAB2IP) is a multidomain scaffold protein and a member of the Ras GTPase-activating protein (RasGAP) family. It acts as a potent tumor suppressor by coordinating a variety of signaling pathways that govern cell growth, survival, and inflammation. DAB2IP functions by inhibiting the Ras-MAPK and PI3K-AKT pathways, which are often overactive in cancer, while simultaneously promoting pro-apoptotic ASK1-JNK signaling and suppressing the pro-inflammatory NF-κB and Wnt/β-catenin pathways. The gene is frequently silenced or downregulated in various aggressive malignancies, particularly prostate, breast, and renal cell carcinomas, primarily through epigenetic mechanisms such as DNA hypermethylation and histone modification by EZH2. Its loss is a major driver of cancer progression, metastasis, and resistance to conventional therapies like cisplatin and radiation. While direct small-molecule activators are not yet in clinical use, DAB2IP remains a key therapeutic interest for its potential in gene therapy and its utility as a prognostic biomarker for treatment resistance.

Other names

AIP1ASK-interacting protein 1AF9Q34KIAA1743DIP1/2DOC-2/DAB2 interactive proteinnGAP-like protein

Functions as a Ras GTPase-activating protein (GAP) to catalyze the hydrolysis of GTP to GDP on Ras proteins, thereby inactivating them; acts as a signaling scaffold to facilitate the activation of ASK1-JNK apoptotic cascades while sequestering and inhibiting AKT and TRAF2.