Structure, function and inhibition of poly(ADP-ribose)polymerase, member 14 (PARP14)

Stephanie S Schweiker*, Amanda Tauber, Madeleine Sherry, Stephan M Levonis

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

25 Citations (Scopus)
618 Downloads (Pure)


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 ADP-ribose (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 anti-inflammatory 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.

Original languageEnglish
Pages (from-to)1659-1669
Number of pages11
JournalMini-Reviews in Medicinal Chemistry
Issue number19
Early online date15 Aug 2018
Publication statusPublished - 2018


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