ADP-ribosylation factor guanine nucleotide exchange factor (ARF-GEF) (ARF-GEF)

ADP-ribosylation factor guanine nucleotide exchange factors (ARF-GEFs) are essential enzymes that regulate the activity of ARF GTPases by facilitating the exchange of bound GDP for GTP (Casanova, 2007, Nature Reviews Molecular Cell Biology). This activation triggers the recruitment of coat proteins to membranes, initiating vesicle budding and regulating membrane trafficking between the Golgi apparatus, endoplasmic reticulum, and plasma membrane (Donaldson & Jackson, 2011, Nature Reviews Molecular Cell Biology). The ARF-GEF family is defined by a conserved catalytic Sec7 domain, which is the primary target for several small-molecule inhibitors (Mouratou et al., 2005, PNAS). In human health, ARF-GEFs play pivotal roles in maintaining cellular homeostasis, and their dysfunction is implicated in cancer progression, particularly in cell invasion and metastasis (Nawaz et al., 2018, Frontiers in Cell and Developmental Biology). Furthermore, many intracellular pathogens, including viruses like poliovirus and bacteria like Legionella, exploit host ARF-GEFs to establish replication niches (Belov et al., 2007, Journal of Virology). While inhibitors like Brefeldin A are powerful research tools, the development of isoform-specific inhibitors is a major focus for therapeutic intervention to minimize toxicity (Wright et al., 2014, Journal of Biological Chemistry).

Other names

ARF guanine nucleotide exchange factorSec7 domain-containing proteinGuanine nucleotide exchange factor for ADP-ribosylation factors

Inhibition of the exchange of GDP for GTP on ARF GTPases by binding to the ARF-GDP-GEF complex, often referred to as interfacial inhibition.