聚（ADP-核糖）聚合酶1（PARP1）在癌症中的转录作用。
Transcriptional roles of PARP1 in cancer.
作者信息
Schiewer Matthew J, Knudsen Karen E
机构信息
Kimmel Cancer Center, Departments of Cancer Biology.
Kimmel Cancer Center, Departments of Cancer Biology, Urology, and Radiation Oncology, Thomas Jefferson University, Philadelphia, Pennsylvania
出版信息
Mol Cancer Res. 2014 Aug;12(8):1069-80. doi: 10.1158/1541-7786.MCR-13-0672. Epub 2014 Jun 10.
Abstract
Poly (ADP-ribose) polymerase-1 (PARP1) is an abundant, ubiquitously expressed NAD(+)-dependent nuclear enzyme that has prognostic value for a multitude of human cancers. PARP1 activity serves to poly (ADP-ribose)-ylate the vast majority of known client proteins and affects a number of cellular and biologic outcomes, by mediating the DNA damage response (DDR), base-excision repair (BER), and DNA strand break (DSB) pathways. PARP1 is also critically important for the maintenance of genomic integrity, as well as chromatin dynamics and transcriptional regulation. Evidence also indicates that PARP-directed therapeutics are "synthetic lethal" in BRCA1/2-deficient model systems. Strikingly, recent studies have unearthed exciting new transcriptional-regulatory roles for PARP1, which has profound implications for human malignancies and will be reviewed herein.
摘要
聚（ADP - 核糖）聚合酶 -1（PARP1）是一种含量丰富、广泛表达的依赖烟酰胺腺嘌呤二核苷酸（NAD⁺）的核酶，对多种人类癌症具有预后价值。PARP1活性用于使绝大多数已知的客户蛋白发生聚（ADP - 核糖）基化，并通过介导DNA损伤反应（DDR）、碱基切除修复（BER）和DNA链断裂（DSB）途径影响许多细胞和生物学结果。PARP1对于维持基因组完整性以及染色质动力学和转录调控也至关重要。有证据还表明，PARP靶向治疗在BRCA1/2缺陷模型系统中具有“合成致死”作用。引人注目的是，最近的研究发现了PARP1令人兴奋的新转录调节作用，这对人类恶性肿瘤具有深远影响，本文将对此进行综述。
相似文献
1
Transcriptional roles of PARP1 in cancer.聚（ADP-核糖）聚合酶1（PARP1）在癌症中的转录作用。
Mol Cancer Res. 2014 Aug;12(8):1069-80. doi: 10.1158/1541-7786.MCR-13-0672. Epub 2014 Jun 10.
2
Common and unique genetic interactions of the poly(ADP-ribose) polymerases PARP1 and PARP2 with DNA double-strand break repair pathways.聚（ADP-核糖）聚合酶PARP1和PARP2与DNA双链断裂修复途径的常见和独特遗传相互作用。
DNA Repair (Amst). 2016 Sep;45:56-62. doi: 10.1016/j.dnarep.2016.06.001. Epub 2016 Jun 16.
3
A Single-Molecule Atomic Force Microscopy Study of PARP1 and PARP2 Recognition of Base Excision Repair DNA Intermediates.单分子原子力显微镜研究 PARP1 和 PARP2 对碱基切除修复 DNA 中间体的识别。
J Mol Biol. 2019 Jul 12;431(15):2655-2673. doi: 10.1016/j.jmb.2019.05.028. Epub 2019 May 23.
4
Mechanistic insight into the role of Poly(ADP-ribosyl)ation in DNA topology modulation and response to DNA damage.聚（ADP-核糖）化在 DNA 拓扑结构调节和 DNA 损伤反应中的作用的机制见解。
Mutagenesis. 2020 Feb 13;35(1):107-118. doi: 10.1093/mutage/gez045.
5
ALC1/CHD1L, a chromatin-remodeling enzyme, is required for efficient base excision repair.ALC1/CHD1L，一种染色质重塑酶，对于有效的碱基切除修复是必需的。
PLoS One. 2017 Nov 17;12(11):e0188320. doi: 10.1371/journal.pone.0188320. eCollection 2017.
6
Poly(ADP-ribose) polymerase 1 regulates activity of DNA polymerase beta in long patch base excision repair.聚（ADP-核糖）聚合酶 1 调节 DNA 聚合酶β在长补丁碱基切除修复中的活性。
Mutat Res. 2010 Mar 1;685(1-2):80-9. doi: 10.1016/j.mrfmmm.2009.08.009. Epub 2009 Aug 22.
7
[Molecular mechanisms of regulaion of transcription by PARP1].[聚（ADP-核糖）聚合酶1对转录调控的分子机制]
Mol Biol (Mosk). 2015 Jan-Feb;49(1):99-113.
8
Chromatin to Clinic: The Molecular Rationale for PARP1 Inhibitor Function.从染色质到临床：PARP1抑制剂功能的分子原理
Mol Cell. 2015 Jun 18;58(6):925-34. doi: 10.1016/j.molcel.2015.04.016.
9
Poly(ADP-ribose) polymerases PARP1 and PARP2 modulate topoisomerase II beta (TOP2B) function during chromatin condensation in mouse spermiogenesis.多聚（ADP-核糖）聚合酶 PARP1 和 PARP2 在小鼠精子发生过程中的染色质浓缩过程中调节拓扑异构酶 IIβ（TOP2B）的功能。
Biol Reprod. 2011 May;84(5):900-9. doi: 10.1095/biolreprod.110.090035. Epub 2011 Jan 12.
10
A novel crosstalk between BRCA1 and poly (ADP-ribose) polymerase 1 in breast cancer.乳腺癌中BRCA1与聚（ADP-核糖）聚合酶1之间的新型相互作用。
Cell Cycle. 2014;13(21):3442-9. doi: 10.4161/15384101.2014.956507.
引用本文的文献
1
PARP1 Inhibition Halts EBV+ Lymphoma Progression by Disrupting the EBNA2/MYC Axis.PARP1抑制通过破坏EBNA2/MYC轴来阻止EBV阳性淋巴瘤的进展。
J Med Virol. 2025 Jul;97(7):e70485. doi: 10.1002/jmv.70485.
2
Cambridge Neoadjuvant Cancer of the Prostate (CANCAP03): A Window Study into the Effects of Olaparib ± Degarelix in Primary Prostate Cancer.剑桥前列腺癌新辅助治疗研究（CANCAP03）：奥拉帕利±地加瑞克对原发性前列腺癌影响的观察性研究
Clin Cancer Res. 2025 Jun 13;31(12):2347-2357. doi: 10.1158/1078-0432.CCR-24-1304.
3
PARP2 Catalytic Activity Is Allosterically Stimulated by Binding to the c-KIT1 G-Quadruplex.PARP2催化活性通过与c-KIT1 G-四链体结合而受到别构激活。
ACS Omega. 2025 Feb 24;10(8):8767-8776. doi: 10.1021/acsomega.5c00724. eCollection 2025 Mar 4.
4
The Landscape of PARP Inhibitors in Solid Cancers.实体癌中PARP抑制剂的研究概况
Onco Targets Ther. 2025 Mar 2;18:297-317. doi: 10.2147/OTT.S499226. eCollection 2025.
5
iNOS-Produced Nitric Oxide from Cancer Cells as an Intermediate of Stemness Regulation by PARP-1 in Colorectal Cancer.癌细胞中诱导型一氧化氮合酶产生的一氧化氮作为PARP-1在结直肠癌中调控干性的中间介质。
Biomolecules. 2025 Jan 14;15(1):125. doi: 10.3390/biom15010125.
6
Potent EGFR/PARP-1 inhibition by spirooxindole-triazole hybrids for targeted liver cancer therapy.螺环氧化吲哚-三唑杂化物对表皮生长因子受体/聚（ADP-核糖）聚合酶-1的强效抑制作用用于靶向肝癌治疗。
RSC Adv. 2025 Jan 3;15(1):58-74. doi: 10.1039/d4ra05966b. eCollection 2025 Jan 2.
7
Poly(ADP-Ribose) Polymerase (PARP) Inhibitors for Cancer Therapy: Advances, Challenges, and Future Directions.聚（ADP-核糖）聚合酶（PARP）抑制剂在癌症治疗中的应用：进展、挑战与未来方向。
Biomolecules. 2024 Oct 9;14(10):1269. doi: 10.3390/biom14101269.
8
Temporal regulation of acetylation status determines PARP1 role in DNA damage response and metabolic homeostasis.乙酰化状态的时间调控决定了 PARP1 在 DNA 损伤反应和代谢稳态中的作用。
Sci Adv. 2024 Oct 18;10(42):eado7720. doi: 10.1126/sciadv.ado7720.
9
Biological Functions and Therapeutic Potential of NAD Metabolism in Gynecological Cancers.NAD代谢在妇科癌症中的生物学功能及治疗潜力
Cancers (Basel). 2024 Sep 5;16(17):3085. doi: 10.3390/cancers16173085.
10
AR coactivators, CBP/p300, are critical mediators of DNA repair in prostate cancer.AR 共激活因子，如 CBP/p300，是前列腺癌中 DNA 修复的关键介质。
Oncogene. 2024 Oct;43(43):3197-3213. doi: 10.1038/s41388-024-03148-4. Epub 2024 Sep 13.
本文引用的文献
1
Phosphorylation of p53 by TAF1 inactivates p53-dependent transcription in the DNA damage response.TAF1 对 p53 的磷酸化在 DNA 损伤反应中使 p53 依赖性转录失活。
Mol Cell. 2014 Jan 9;53(1):63-74. doi: 10.1016/j.molcel.2013.10.031. Epub 2013 Nov 27.
2
Targeting PARP-1 allosteric regulation offers therapeutic potential against cancer.靶向 PARP-1 的变构调节为癌症治疗提供了潜在可能。
Cancer Res. 2014 Jan 1;74(1):31-7. doi: 10.1158/0008-5472.CAN-13-1701. Epub 2013 Nov 4.
3
Proteome-wide identification of poly(ADP-Ribosyl)ation targets in different genotoxic stress responses.在不同的遗传毒性应激反应中对多聚（ADP-核糖）化靶标的蛋白质组学鉴定。
Mol Cell. 2013 Oct 24;52(2):272-85. doi: 10.1016/j.molcel.2013.08.026. Epub 2013 Sep 19.
4
Site-specific characterization of the Asp- and Glu-ADP-ribosylated proteome.针对天冬氨酸和谷氨酸 ADP-核糖基化蛋白质组的特异性研究。
Nat Methods. 2013 Oct;10(10):981-4. doi: 10.1038/nmeth.2603. Epub 2013 Aug 18.
5
Tripartite Motif-containing 33 (TRIM33) protein functions in the poly(ADP-ribose) polymerase (PARP)-dependent DNA damage response through interaction with Amplified in Liver Cancer 1 (ALC1) protein.三结构域蛋白 33（TRIM33）蛋白通过与肝癌扩增蛋白 1（ALC1）蛋白相互作用，在聚（ADP-核糖）聚合酶（PARP）依赖性 DNA 损伤反应中发挥作用。
J Biol Chem. 2013 Nov 8;288(45):32357-32369. doi: 10.1074/jbc.M113.459164. Epub 2013 Aug 6.
6
The recognition and removal of cellular poly(ADP-ribose) signals.细胞多聚（ADP-核糖）信号的识别与清除。
FEBS J. 2013 Aug;280(15):3491-507. doi: 10.1111/febs.12358. Epub 2013 Jun 18.
7
DNA double-strand breaks coupled with PARP1 and HNRNPA2B1 binding sites flank coordinately expressed domains in human chromosomes.DNA 双链断裂与 PARP1 和 HNRNPA2B1 结合位点一起位于人类染色体上协调表达的结构域的两侧。
PLoS Genet. 2013 Apr;9(4):e1003429. doi: 10.1371/journal.pgen.1003429. Epub 2013 Apr 4.
8
Deficiency of terminal ADP-ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease.神经退行性疾病中末端 ADP-核糖蛋白糖基水解酶 TARG1/C6orf130 的缺乏。
EMBO J. 2013 May 2;32(9):1225-37. doi: 10.1038/emboj.2013.51. Epub 2013 Mar 12.
9
Interaction between PARP-1 and HIF-2α in the hypoxic response.PARP-1 与 HIF-2α 在低氧反应中的相互作用。
Oncogene. 2014 Feb 13;33(7):891-8. doi: 10.1038/onc.2013.9. Epub 2013 Mar 4.
10
Reprogramming cellular events by poly(ADP-ribose)-binding proteins.通过聚（ADP-核糖）结合蛋白重编程细胞事件。
Mol Aspects Med. 2013 Dec;34(6):1066-87. doi: 10.1016/j.mam.2012.12.005. Epub 2012 Dec 23.
Zotero 插件