Rho GDP Dissociation Inhibitor Beta (RhoGDIβ), also known as ARHGDIB, is a protein that plays a crucial role in the regulation of the Rho family of GTPases. These GTPases are involved in various cellular processes, including cell signaling, proliferation, cytoskeletal organization, and secretion. The RhoGDIβ protein is encoded by the ARHGDIB gene in humans .
The ARHGDIB gene is located on chromosome 12 and is a protein-coding gene. The protein encoded by this gene is involved in the regulation of the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them . This regulation is essential for maintaining the proper function of Rho GTPases, which act as molecular switches in various cellular processes .
RhoGDIβ regulates the actin cytoskeleton by binding to the GTP-bound form of Rho and preventing the activation of Rac1 by dissociating it from its activators . The inhibitory activity of RhoGDIβ derives from its ability to bind the carboxy-terminal isoprene of Rho GTPases and extract them from membranes, as well as from inhibiting the GTPase cycling between the GTP- and GDP-bound states .
RhoGDIβ is involved in several critical cellular pathways, including signaling by Rho GTPases and apoptosis and survival FAS signaling cascades . It plays a significant role in the reorganization of the actin cytoskeleton mediated by Rho family members . This protein is also associated with various diseases, such as ovarian cancer and muscular dystrophy-dystroglycanopathy .
The functional role of RhoGDIβ in tumor biology appears to be contradictory across various studies. For instance, in the context of bladder cancer, RhoGDIβ expression patterns and biological functions vary depending on the stage of carcinogen exposure. It has been observed that RhoGDIβ inhibits the transformation of human urothelial cells during the early phase of exposure to bladder carcinogens, whereas it promotes invasion of the transformed/progressed urothelial cells in the late stage of exposure . This dual role suggests that RhoGDIβ may serve as a useful biomarker for evaluating the progression of human bladder cancers .