Ral binding protein 1 (RLIP76) is a multifunctional protein that transports glutathione–electrophile conjugates as well as chemotherapy drugs across the plasmalemma.
It is also required for diverse cellular functions such as mitosis, apoptosis and endocytosis and is overexpressed in a variety of malignancies
The GTPase activating protein RLIP76 is overexpressed in and correlates with the pathological grade of many malignant tumor cells.
It is a central regulator in multiple pathways that respond to redox states and control cell growth, motility, division, and apoptosis in many malignant cancer cells.
The dramatic increases in cancer cell radio- and chemosensitivity induced by RNAi-mediated RLIP76 knockdown and RLIP76 antibody inhibition are mainly due to suppression of RLIP76 adenosine triphosphatase (ATPase)-dependent transporter activity, allowing accumulation of endogenously formed glutathione–electrophile conjugates and drugs that induce apoptosis in cancer cells. In addition to membrane transport, RLIP76 is a Rho-selective GTPase-activating protein (RhoGAP) and negative regulator of Cdc42 and Rac1 1).
Inhibition of RLIP76 expression may be an effective means for overcoming RLIP76-associated chemoresistance in human malignant glioma cells and may represent a potential gene-targeting approach for glioma treatment 2).
RLIP76 expression is associated with a poor outcome of meningioma and may provide a new gene therapy approach for patients with malignant meningiomas 3).