Rab interacting factor (RABIF)

Rab interacting factor (RABIF) is a highly conserved, soluble protein that acts as a crucial chaperone for Rab GTPases, maintaining their stability and preventing their degradation. While originally described as a guanine nucleotide exchange factor (GEF), more recent studies have demonstrated that RABIF functions predominantly as a holdase chaperone, ensuring proper folding and cellular levels of multiple Rab proteins involved in vesicular trafficking, such as Rab10, Rab8, and Rab13. This function is vital for processes like insulin-stimulated GLUT4 exocytosis in adipocytes, where RABIF deficiency results in defective exocytosis and glucose uptake. Beyond its role in vesicle transport, RABIF expression is dynamically regulated by cellular stress and contributes to cell survival by modulating the JNK MAPK pathway and inhibiting apoptosis. Aberrant overexpression of RABIF has been linked to tumor progression in hepatocellular carcinoma, in part via regulation of mitophagy and glucose metabolism pathways, identifying it as a potential therapeutic target.

Other names

MSS4RASGRF3RASGFR3mss4mammalian suppressor of SEC4Rab-interacting factorguanine nucleotide exchange factor MSS4Ras-specific guanine-releasing factor 3

Chaperone-mediated stabilization of Rab GTPases (e.g., Rab10, Rab8, Rab13). Anti-apoptotic effect via interaction with stress response/apoptosis signaling pathways. Putative role in therapeutic sensitization to kinase inhibitors (e.g., sorafenib).