PARP 酶和单 ADP 核糖基化：推进干扰素信号传导与癌症生物学的联系。
PARP enzymes and mono-ADP-ribosylation: advancing the connection from interferon-signalling to cancer biology.
发表日期：2024 Aug 27
作者：
Barbara Morone, Giovanna Grimaldi
来源：
EXPERT REVIEWS IN MOLECULAR MEDICINE
摘要：
PARP 家族的 ADP-核糖基转移酶包含一组在细胞中具有多种调节功能的酶，范围从 DNA 损伤修复到细胞周期进程和免疫反应的控制。多年来，这一知识导致使用 PARP1/2 抑制剂作为治疗卵巢癌、胰腺癌、前列腺癌和乳腺癌的主要药物策略，使编码参与 DNA 修复机制（合成致死）的蛋白质的基因发生突变。 。与此同时，过去十年在理解单 ADP 核糖基化调节的细胞通路方面取得了重大进展，并在开发新型选择性化合物来抑制具有单 ADP 核糖基化活性的 PARP 方面做出了巨大努力。本综述重点关注癌症领域取得的进展，深入探讨了有关酶子集（干扰素刺激的 PARP）在癌症进展中的作用的最新发现。
ADP-ribosyltransferases of the PARP family encompass a group of enzymes with variegated regulatory functions in cells, ranging from DNA damage repair to the control of cell-cycle progression and immune response. Over the years, this knowledge has led to the use of PARP1/2 inhibitors as mainstay pharmaceutical strategies for the treatment of ovarian, pancreatic, prostate and breast cancers, holding mutations in genes encoding for proteins involved in the DNA repair mechanisms (synthetic lethality). Meanwhile, the last decade has witnessed significant progress in comprehending cellular pathways regulated by mono-ADP-ribosylation, with a huge effort in the development of novel selective compounds to inhibit those PARPs endowed with mono-ADP-ribosylation activity. This review focuses on the progress achieved in the cancer field, delving into most recent findings regarding the role of a subset of enzymes - the interferon-stimulated PARPs - in cancer progression.