用于癌症治疗的新型聚（ADP - 核糖）聚合酶靶点。
New PARP targets for cancer therapy.
作者信息
Vyas Sejal, Chang Paul
机构信息
Koch Institute for Integrative Cancer Research and the Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
出版信息
Nat Rev Cancer. 2014 Jul;14(7):502-9. doi: 10.1038/nrc3748. Epub 2014 Jun 5.
Abstract
Poly(ADP-ribose) polymerases (PARPs) modify target proteins post-translationally with poly(ADP-ribose) (PAR) or mono(ADP-ribose) (MAR) using NAD(+) as substrate. The best-studied PARPs generate PAR modifications and include PARP1 and the tankyrase PARP5A, both of which are targets for cancer therapy with inhibitors in either clinical trials or preclinical development. There are 15 additional PARPs, most of which modify proteins with MAR, and their biology is less well understood. Recent data identify potentially cancer-relevant functions for these PARPs, which indicates that we need to understand more about these PARPs to effectively target them.
摘要
聚（ADP-核糖）聚合酶（PARP）以烟酰胺腺嘌呤二核苷酸（NAD⁺）为底物，通过聚（ADP-核糖）（PAR）或单（ADP-核糖）（MAR）对靶蛋白进行翻译后修饰。研究最深入的PARP可产生PAR修饰，包括PARP1和端锚聚合酶PARP5A，在临床试验或临床前开发中，这两种酶都是癌症治疗抑制剂的靶点。另外还有15种PARP，其中大多数用MAR修饰蛋白质，对它们生物学特性的了解较少。最新数据确定了这些PARP潜在的与癌症相关的功能，这表明我们需要更多地了解这些PARP，以便有效地将它们作为靶点。
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