Qin Wei, Wu Hong-Jie, Cao Lu-Qi, Li Hui-Jin, He Chun-Xia, Zhao Dong, Xing Lu, Li Peng-Quan, Jin Xi, Cao Hui-Ling
Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Shaanxi Key Laboratory of Brain disorders, Institute of Basic and Translational Medicine, Xi'an Medical University, Xi'an, China.
Front Pharmacol. 2019 Mar 5;10:172. doi: 10.3389/fphar.2019.00172. eCollection 2019.
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.
聚腺苷二磷酸核糖聚合酶（PARP）对靶蛋白进行翻译后单或多聚ADP核糖基化修饰。在庞大的PARP酶家族已知的18个成员中，过去几十年对PARP1、PARP2和PARP5a/5b进行了多项研究；更具体地说，PARP14正逐渐成为一个有前景的药物靶点。完整的PARP14（也称为ARTD8或BAL2）由macro1、macro2、macro3、WWE和催化结构域组成。PARP14利用烟酰胺腺嘌呤二核苷酸（NAD）作为代谢底物对靶蛋白进行单ADP核糖基化修饰，参与免疫系统中的细胞反应和信号通路。因此，PARP14被认为是治疗肿瘤和过敏性炎症的一个有吸引力的靶点。更重要的是，基于合成致死理论及其在同源重组DNA修复中的独特作用，PARP14可能成为化学增敏剂的潜在靶点。本文首先简要介绍了几个有代表性的PARP成员。随后，呈现当前文献以揭示PARP14作为癌症（如弥漫性大B细胞淋巴瘤、多发性骨髓瘤、前列腺癌和肝细胞癌）和过敏性炎症新型药物靶点的分子机制。最后，讨论了PARP抑制剂相关的潜在不良反应。该综述可为针对PARP14的创新药物或化学增敏剂的发现提供有意义的参考。
