DAB2IP

DAB2IP stands for DAB2 interacting protein and refers to a cytoplasmic signaling protein encoded by the DAB2IP gene on chromosome 9q33-34. It is a Ras-GAP–like protein that contains multiple conserved domains, including a C2 domain, a PH domain, and a Ras-GAP–related domain, enabling it to modulate signaling pathways and act as a scaffolding protein in various cellular processes.

Functionally, DAB2IP serves as a tumor suppressor by negatively regulating Ras signaling and modulating pathways that control cell survival and apoptosis. It promotes stress-induced apoptosis through the ASK1–JNK pathway and can influence NF-kB signaling, thereby impacting inflammatory responses and cell fate decisions. Through these interactions, DAB2IP helps balance proliferation and death signals in cells and can influence sensitivity to stressors such as cytokines.

Regulation of DAB2IP is frequently disrupted in cancer. The gene is commonly downregulated or silenced by promoter hypermethylation in several tumor types, including prostate, breast, colorectal, and hepatocellular carcinomas. Loss of DAB2IP correlates with enhanced tumor progression, metastasis, therapy resistance, and poor clinical outcomes. Conversely, restoration of DAB2IP expression can suppress tumor growth and increase susceptibility to apoptosis and radiotherapy in cancer cells, highlighting its potential as a therapeutic target.

Clinical and research interest in DAB2IP includes its potential use as a prognostic biomarker based on methylation status and expression levels, as well as its value in understanding how Ras- and stress-related signaling networks influence cancer development and treatment response. The protein interacts with DAB2 and components of the ASK1 signaling module, and exists in multiple splice variants that may have tissue-specific roles.