Research Progress on PARP14 as a Drug Target

Abstract

Poly-adenosine diphosphate-ribose polymerase (PARP) implements posttranslational mono- or poly-ADP-ribosylation modification of target proteins. Among the known 18 members in the enormous family of PARP enzymes, several investigations about PARP1, PARP2, and PARP5a/5b have been launched in the past few decades; more specifically, PARP14 is gradually emerging as a promising drug target. An intact PARP14 (also named ARTD8 or BAL2) is constructed by macro1, macro2, macro3, WWE, and the catalytic domain. PARP14 takes advantage of nicotinamide adenine dinucleotide (NAD+) as a metabolic substrate to conduct mono-ADP-ribosylation modification on target proteins, taking part in cellular responses and signaling pathways in the immune system. Therefore, PARP14 has been considered a fascinating target for treatment of tumors and allergic inflammation. More importantly, PARP14 could be a potential target for a chemosensitizer based on the theory of synthetic lethality and its unique role in homologous recombination DNA repair. This review first gives a brief introduction on several representative PARP members. Subsequently, current literatures are presented to reveal the molecular mechanisms of PARP14 as a novel drug target for cancers (e.g., diffuse large B-cell lymphoma, multiple myeloma, prostate cancer, and hepatocellular carcinoma) and allergic inflammatory. Finally, potential PARP inhibitor-associated adverse effects are discussed. The review could be a meaningful reference for innovative drug or chemosensitizer discovery targeting to PARP14.

Evolution of Advanced Chronic Lymphoid Leukemia Unveiled by Single-Cell Transcriptomics: A Case Report

“…Interestingly, the gene that showed the highest significance was PARP14 ( Figure S1E). This has been previously reported to play a role in chemoresistance (17). Our analysis also highlighted one gene (ZNF292) showing lower expression in the relapseenriched clone and that was significantly correlated to poorer prognosis of tumors displaying low expression.…”

Mapping physiological ADP-ribosylation using Activated Ion Electron Transfer Dissociation (AI-ETD)

“…In case of PARP14, physiological ADPribosylation only targeted tyrosine residues, similarly setting it apart from PARP1 and PARP2 which were primarily modified on serine residues. Auto-modification of PARP14 has been described previously (Qin et al, 2019), and the interactome of PARP14 suggests a role in regulating RNA stability (Carter-O'Connell et al, 2018). We detected modification of PARP13 in cells on one cysteine residue, and PARP14 has been demonstrated to MARylate PARP13 in vitro (Carter-O'Connell et al, 2018), although there acidic amino acids were targeted for modification.…”

The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions

“…PARPs have been targets for drug development, particularly in the cancer field. The most active targets include PARP1, and more recently PARP14 (Berger et al 2018;Qin et al 2019). Studies that used the small molecule inhibitors demonstrated that PARP suppression reduces proinflammatory responses or enhances anti-inflammatory functions of macrophages (Haskó et al 2002;Wang et al 2013;Shrestha et al 2016;Dharwal et al 2019).…”