Poly [ADP-ribose] polymerase 8 (PARP8)

Poly [ADP-ribose] polymerase 8 (PARP8), also known as Mono-ADP-ribosyltransferase 8 or ARTD16, is an enzyme belonging to the PARP family that localizes primarily to the nuclear envelope (UniProt Q8N3A1). Unlike the well-known PARP1, PARP8 functions as a mono-ADP-ribosyltransferase, catalyzing the transfer of a single ADP-ribose unit from NAD+ onto target proteins rather than forming long polymer chains (PubMed: 28235823). It plays a significant role in maintaining the structural integrity of the nuclear pore complex and is involved in regulating the cell cycle and cellular stress responses (PubMed: 28235823). While not the primary intended target of clinical PARP inhibitors like Olaparib or Niraparib, PARP8 has been identified as a relevant off-target for several of these agents, particularly Niraparib, which inhibits it with nanomolar potency (PubMed: 24598386). This off-target activity may contribute to the overall therapeutic profile or the side effects observed with non-selective PARP inhibitors. Research into PARP8 is ongoing to determine its specific contributions to oncogenesis and its potential as a selective therapeutic target in cancer and viral infections.

Other names

ARTD16Mono-ADP-ribosyltransferase 8ADP-ribosyltransferase diphtheria toxin-like 16pART8

Competitive inhibition of the catalytic domain by binding to the NAD+ binding site, preventing the mono-ADP-ribosylation of target proteins (PubMed: 24598386).