ADP-ribosylation factor regulatory proteins (Arf regulatory proteins)

ADP-ribosylation factor (Arf) regulatory proteins are a broad class of enzymes that modulate the activity of Arf GTPases, which are critical for intracellular membrane trafficking and actin cytoskeleton organization (Nature Reviews Molecular Cell Biology, 2011). This group encompasses two primary functional types: guanine nucleotide exchange factors (GEFs) that activate Arf proteins by facilitating the exchange of GDP for GTP, and GTPase-activating proteins (GAPs) that inactivate them by accelerating GTP hydrolysis (Journal of Biological Chemistry, 2023). Prominent examples include the cytohesin family (e.g., ARNO), GBF1, and the BIG family of GEFs, as well as the ASAP and ACAP families of GAPs (Nature Reviews Molecular Cell Biology, 2011). These regulatory proteins are frequently dysregulated in human diseases, particularly in cancer, where they promote tumor cell invasion, migration, and epithelial-mesenchymal transition (MedComm, 2025). They also play significant roles in viral and bacterial infections by facilitating the assembly of viral replication complexes or the entry of pathogens (Journal of Biological Chemistry, 2023). Small molecule inhibitors like Brefeldin A and SecinH3 have been developed to target specific Arf GEFs, demonstrating potential for therapeutic intervention in oncology and infectious diseases (Journal of Biological Chemistry, 2023). However, the fundamental role of Arf signaling in basic cellular processes like Golgi maintenance presents a significant challenge for achieving a favorable safety profile in clinical applications (Journal of Biological Chemistry, 2023).

Other names

Arf GEFsArf GAPsArf guanine nucleotide exchange factorsArf GTPase-activating proteinsArf regulatorsADP-ribosylation factor GEFsADP-ribosylation factor GAPs

Inhibition of guanine nucleotide exchange factors (GEFs) or modulation of GTPase-activating proteins (GAPs) to regulate Arf GTPase activity.