ADP-ribosylation factor 6 (ARF6) (ARF6)

ADP-ribosylation factor 6 (ARF6) is a small GTP-binding protein belonging to the Ras superfamily that serves as a master regulator of membrane trafficking and actin cytoskeleton reorganization at the cell periphery (UniProt P62330). Unlike other ARF isoforms that operate within the Golgi complex, ARF6 specifically coordinates the movement of membranes between the plasma membrane and intracellular endosomal compartments, facilitating endocytosis, exocytosis, and the recycling of cell surface receptors (PubMed: 22492361). In disease states, particularly cancer, ARF6 is often hyperactivated, where it promotes tumor cell invasion and metastasis by mobilizing integrins and stimulating matrix metalloproteinase activity (PubMed: 17510406). It also plays a pivotal role in vascular permeability and inflammatory signaling, making it a target of interest for treating solid tumors and exudative retinopathies (PubMed: 24821989). Therapeutic strategies currently focus on small molecule inhibitors that prevent ARF6 activation by its guanine nucleotide exchange factors (GEFs) or directly block its GTP-binding site.

Other names

ARF6ADP-ribosylation factor 6Small GTPase ARF6

Inhibition of ARF6 activation by blocking guanine nucleotide exchange factors (GEFs) or direct inhibition of GTP binding to the ARF6 protein.