Mono-ADP-ribosyltransferase 1 (ART1)

Mono-ADP-ribosyltransferase 1 (ART1) is a glycosylphosphatidylinositol (GPI)-anchored enzyme primarily located on the extracellular surface of the plasma membrane (UniProt P52961). It catalyzes the post-translational modification known as mono-ADP-ribosylation, transferring an ADP-ribose group from nicotinamide adenine dinucleotide (NAD+) to specific arginine residues on target proteins (PubMed: 28416595). This modification regulates the function of several key cell-surface molecules, including the P2X7 purinergic receptor and various integrins, which are involved in cell death signaling and adhesion (PubMed: 32433948). In the field of oncology, ART1 has emerged as a significant therapeutic target because it is overexpressed in certain cancers, such as non-small cell lung cancer (NSCLC), where it facilitates immune evasion by ADP-ribosylating P2X7 on tumor-infiltrating T cells, leading to their apoptosis (Science Translational Medicine, 2020). Consequently, blocking ART1 activity with small molecules or monoclonal antibodies is being explored as a strategy to enhance anti-tumor immunity and improve the efficacy of existing immunotherapies. Beyond its role in cancer, ART1 is also expressed in skeletal and cardiac muscle, where it contributes to normal physiological processes and differentiation.

Other names

ADP-ribosyltransferase C2 and C3 toxin-like 1ARTC1CD296RT6-related proteinMono-ADP-ribosyltransferase-1

Inhibition of the enzymatic transfer of an ADP-ribose moiety from NAD+ to arginine residues on extracellular target proteins, such as the P2X7 receptor or integrins, to modulate cell signaling and immune responses.