PARP enzymes and mono-ADP-ribosylation: advancing the connection from interferon-signalling to cancer biology.

IF 4.5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Expert Reviews in Molecular Medicine Pub Date : 2024-08-27 DOI:10.1017/erm.2024.13
Barbara Morone, Giovanna Grimaldi
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Abstract

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.

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PARP酶和单ADP-核糖基化:推进从干扰素信号到癌症生物学的联系。
PARP 家族的 ADP 核糖转移酶包括一组在细胞中具有各种调节功能的酶,从 DNA 损伤修复到控制细胞周期进展和免疫反应。多年来,这些知识促使人们将 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,因为 DNA 修复机制(合成致死)涉及的蛋白质编码基因发生了突变。与此同时,在过去十年中,人们在理解受单 ADP 核糖基化调控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以抑制具有单 ADP 核糖基化活性的 PARPs 方面做出了巨大努力。本综述将重点关注癌症领域取得的进展,深入探讨有关干扰素刺激的 PARPs 这一类酶在癌症进展中所起作用的最新发现。
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来源期刊
Expert Reviews in Molecular Medicine
Expert Reviews in Molecular Medicine BIOCHEMISTRY & MOLECULAR BIOLOGY-MEDICINE, RESEARCH & EXPERIMENTAL
CiteScore
7.40
自引率
1.60%
发文量
45
期刊介绍: Expert Reviews in Molecular Medicine is an innovative online journal featuring authoritative and timely Reviews covering gene therapy, immunotherapeutics, drug design, vaccines, genetic testing, pathogenesis, microbiology, genomics, molecular epidemiology and diagnostic techniques. We especially welcome reviews on translational aspects of molecular medicine, particularly those related to the application of new understanding of the molecular basis of disease to experimental medicine and clinical practice.
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