Poly(ADP-ribose)polymerase, member 14 (PARP14, alternatively named ARTD8, BAL2,
and COAST6) is an intracellular mono(ADP-ribosyl) transferase. PARP14 transfers a negatively
charged ADP-ribose unit from a donor NAD+ molecule onto a target protein, post-translationally.
PARP14’s domain architecture consists of three macrodomains (Macro1, Macro2 and Macro3), a
WWE domain and an ARTD (or catalytic domain). The Macro2 and Macro3 domains bind ADPribose
(ADPr) with high affinity, whereas the WWE domain stabilizes the protein structure by binding
to ADPr derivatives. The catalytic domain is involved in binding the NAD+ and catalyzing the mono-
ADP-ribosylation reaction. PARP14 has been identified as a possible anti-cancer and antiinflammatory
target. Acting as a transcriptional co-activator for STAT6, PARP14 acts to promote the
over activation of the Th2 immune response, thus promoting the metabolic change to an anaerobic
state (Warburg effect) and activation of cell survival pathways through JNK2 and the PGI/AMF complex.
These changes are consistent with the metabolic sophistication observed in cancer, and the immune
imbalance in inflammatory diseases. Current literature on selective and unselective PARP14 inhibitors
are reviewed and discussed. Although there is no evidence that selective PARP inhibitors
would be advantageous we have proposed some strategies for future design of selective PARP14 inhibitors.
Keywords: PARP14, cancer, inhibitors, ARTD8, BAL2, COAST6, MAR, ARTD.
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