Drel' V R, Shymans'kyĭ I O, Sybirna N O, Velykyĭ M M
Ukr Biokhim Zh (1999). 2011 Nov-Dec;83(6):5-34.
This review focuses on the biological role of enzymes involved in posttranslational modification of proteins by their poly-ADP-ribosylation, a NAD-consuming process with an emerging key role in providing fundamental cell functions. To this end, detailed analysis of structural organization in relation to basic functions of the poly(ADP-ribose) polymerase-1 (PARP-1), the founding member of the PARP family, and other poly(ADP-ribose) polymerase isoforms is presented here. These include the current views on the role of PARP family enzymes and processes of poly-ADP-ribosylation of proteins in chromatin structure remodeling, DNA damage repair, regulation of gene expression, and integration of cellular signaling pathways. Considerable attention is paid to the involvement of PARP in cellular functions, particularly in cell division, intracellular transport of macromolcules, proteasomal protein degradation, immune response and caspase-independent necrotic pathways defined as necroptosis (programmed necrosis). In the light of the remarkable successes that have been reported for treating inflammatory disorders and cancer with different classes of PARPs inhibitors, we discuss the prospects of targeting PARPs with therapeutic purposes.
本综述聚焦于通过蛋白质的多聚ADP核糖基化参与蛋白质翻译后修饰的酶的生物学作用，这是一个消耗NAD的过程，在提供基本细胞功能方面发挥着新出现的关键作用。为此，本文详细分析了聚（ADP - 核糖）聚合酶 - 1（PARP - 1）（PARP家族的创始成员）及其他聚（ADP - 核糖）聚合酶同工型的结构组织与其基本功能的关系。这些内容包括目前对PARP家族酶的作用以及蛋白质多聚ADP核糖基化过程在染色质结构重塑、DNA损伤修复、基因表达调控和细胞信号通路整合中的看法。文中特别关注了PARP在细胞功能中的参与情况，尤其是在细胞分裂、大分子的细胞内运输、蛋白酶体蛋白降解、免疫反应以及定义为坏死性凋亡（程序性坏死）的半胱天冬酶非依赖性坏死途径中的作用。鉴于已报道的使用不同类别的PARP抑制剂治疗炎症性疾病和癌症取得的显著成功，我们讨论了以治疗为目的靶向PARP的前景。
