FH 缺陷型 2 型乳头状肾细胞癌中 Keap1 的琥珀酰化和 Nrf2 依赖性抗氧化途径的激活。
Succination of Keap1 and activation of Nrf2-dependent antioxidant pathways in FH-deficient papillary renal cell carcinoma type 2.
机构信息
Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
出版信息
Cancer Cell. 2011 Oct 18;20(4):418-20. doi: 10.1016/j.ccr.2011.10.005.
Abstract
Fumarate hydratase (FH) is a tumor suppressor, but how it acts is unclear. Two reports in this issue of Cancer Cell reveal that FH deficiency leads to succination of Keap1, stabilization of Nrf2, and induction of stress-response genes including HMOX1, which is important for the survival of FH-deficient cells.
摘要
琥珀酸脱氢酶（FH）是一种肿瘤抑制因子，但它的作用机制尚不清楚。本期《癌细胞》杂志的两篇报道揭示，FH 缺陷导致 Keap1 的琥珀酰化、Nrf2 的稳定，以及应激反应基因（包括对 FH 缺陷细胞的存活很重要的 HMOX1）的诱导。
相似文献
1
Succination of Keap1 and activation of Nrf2-dependent antioxidant pathways in FH-deficient papillary renal cell carcinoma type 2.FH 缺陷型 2 型乳头状肾细胞癌中 Keap1 的琥珀酰化和 Nrf2 依赖性抗氧化途径的激活。
Cancer Cell. 2011 Oct 18;20(4):418-20. doi: 10.1016/j.ccr.2011.10.005.
2
Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status.琥珀酰化蛋白在富马酸水合酶缺陷型小鼠和 HLRCC 患者中的异常是突变状态的一个强有力的生物标志物。
J Pathol. 2011 Sep;225(1):4-11. doi: 10.1002/path.2932. Epub 2011 Jun 1.
3
Advances in hereditary leiomyomatosis and renal cell carcinoma (HLRCC) research.遗传性平滑肌瘤病和肾细胞癌（HLRCC）研究进展。
Semin Cancer Biol. 2020 Apr;61:158-166. doi: 10.1016/j.semcancer.2019.10.016. Epub 2019 Nov 2.
4
A Rare Case of Synchronous Fumarate Hydratase-Deficient Renal Cell Carcinoma and Clear Cell Renal Cell Carcinoma With Fumarate Hydratase and von Hippel-Lindau Gene Mutations: A Clinicopathologic and Molecular Study.一例罕见的琥珀酸脱氢酶缺陷型肾细胞癌合并透明细胞肾细胞癌，伴琥珀酸脱氢酶和 von Hippel-Lindau 基因突变：临床病理和分子研究。
Int J Surg Pathol. 2024 Jun;32(4):810-816. doi: 10.1177/10668969231195072. Epub 2023 Sep 16.
5
Inhibition of mitochondrial aconitase by succination in fumarate hydratase deficiency.琥珀酸脱水酶缺乏时琥珀酸导致的线粒体 aconitase 抑制。
Cell Rep. 2013 Mar 28;3(3):689-700. doi: 10.1016/j.celrep.2013.02.013. Epub 2013 Mar 14.
6
P4HB, a novel succinated protein, is essential for fumarate-induced cancer metastasis.P4HB是一种新型琥珀酸化蛋白，对富马酸酯诱导的癌症转移至关重要。
Int J Biol Macromol. 2025 Jun;311(Pt 3):143885. doi: 10.1016/j.ijbiomac.2025.143885. Epub 2025 May 1.
7
Fumarate inhibits PTEN to promote tumorigenesis and therapeutic resistance of type2 papillary renal cell carcinoma.富马酸盐抑制 PTEN 以促进 2 型乳头状肾细胞癌的肿瘤发生和治疗耐药性。
Mol Cell. 2022 Apr 7;82(7):1249-1260.e7. doi: 10.1016/j.molcel.2022.01.029. Epub 2022 Feb 24.
8
Fumarate Hydratase-deficient Renal Cell Carcinoma Is Strongly Correlated With Fumarate Hydratase Mutation and Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome.延胡索酸水合酶缺陷型肾细胞癌与延胡索酸水合酶突变及遗传性平滑肌瘤病和肾细胞癌综合征密切相关。
Am J Surg Pathol. 2016 Jul;40(7):865-75. doi: 10.1097/PAS.0000000000000617.
9
Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling.Fh1 缺陷型小鼠肾囊肿的形成不依赖于 Hif/Phd 通路：富马酸盐在 KEAP1 琥珀酰化和 Nrf2 信号中的作用。
Cancer Cell. 2011 Oct 18;20(4):524-37. doi: 10.1016/j.ccr.2011.09.006.
10
[Clinicopathological features and prognosis of fumarate hydratase deficient renal cell carcinoma].富马酸水合酶缺乏性肾细胞癌的临床病理特征及预后
Beijing Da Xue Xue Bao Yi Xue Ban. 2021 Aug 18;53(4):640-646. doi: 10.19723/j.issn.1671-167X.2021.04.003.
引用本文的文献
1
Inhibition of HDAC6 alters fumarate hydratase activity and mitochondrial structure.组蛋白去乙酰化酶6的抑制作用会改变延胡索酸水合酶活性和线粒体结构。
Nat Commun. 2025 Jul 28;16(1):6923. doi: 10.1038/s41467-025-61897-6.
2
Dimethyl fumarate modulates M1/M2 macrophage polarization to ameliorate periodontal destruction by increasing TUFM-mediated mitophagy.富马酸二甲酯通过增加TUFM介导的线粒体自噬来调节M1/M2巨噬细胞极化，从而改善牙周组织破坏。
Int J Oral Sci. 2025 Apr 17;17(1):32. doi: 10.1038/s41368-025-00360-0.
3
Health position paper and redox perspectives - Bench to bedside transition for pharmacological regulation of NRF2 in noncommunicable diseases.健康立场文件与氧化还原观点——非传染性疾病中NRF2药理调节从 bench 到床边的转化
Redox Biol. 2025 Apr;81:103569. doi: 10.1016/j.redox.2025.103569. Epub 2025 Mar 3.
4
Nrf2 Signaling in Renal Cell Carcinoma: A Potential Candidate for the Development of Novel Therapeutic Strategies.肾细胞癌中的Nrf2信号通路：新型治疗策略开发的潜在候选对象
Int J Mol Sci. 2024 Dec 10;25(24):13239. doi: 10.3390/ijms252413239.
5
Mechanism of Endometrial Receptivity Affected by Fibroids.子宫肌瘤影响子宫内膜容受性的机制
Am J Reprod Immunol. 2024 Dec;92(6):e70022. doi: 10.1111/aji.70022.
6
Cholesterol accumulation impairs HIF-1α-dependent immunometabolic reprogramming of LPS-stimulated macrophages by upregulating the NRF2 pathway.胆固醇积累通过上调 NRF2 通路损害 LPS 刺激的巨噬细胞中 HIF-1α 依赖性免疫代谢重编程。
Sci Rep. 2024 May 15;14(1):11162. doi: 10.1038/s41598-024-61493-6.
7
Hepatic malonyl-CoA synthesis restrains gluconeogenesis by suppressing fat oxidation, pyruvate carboxylation, and amino acid availability.肝酰基辅酶 A 的合成通过抑制脂肪氧化、丙酮酸羧化和氨基酸可用性来抑制糖异生。
Cell Metab. 2024 May 7;36(5):1088-1104.e12. doi: 10.1016/j.cmet.2024.02.004. Epub 2024 Mar 5.
8
The immunometabolic ecosystem in cancer.癌症中的免疫代谢生态系统。
Nat Immunol. 2023 Dec;24(12):2008-2020. doi: 10.1038/s41590-023-01675-y. Epub 2023 Nov 27.
9
The Pleiotropic Effects of Fumarate: From Mitochondrial Respiration to Epigenetic Rewiring and DNA Repair Mechanisms.富马酸盐的多效性作用：从线粒体呼吸到表观遗传重编程和DNA修复机制
Metabolites. 2023 Jul 24;13(7):880. doi: 10.3390/metabo13070880.
10
Reporting on FH-deficient renal cell carcinoma using circulating succinylated metabolites.应用循环琥珀酰化代谢物报告 FH 缺陷型肾细胞癌。
J Clin Invest. 2023 Jun 1;133(11):e170195. doi: 10.1172/JCI170195.
本文引用的文献
1
Renal cyst formation in Fh1-deficient mice is independent of the Hif/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling.Fh1 缺陷型小鼠肾囊肿的形成不依赖于 Hif/Phd 通路：富马酸盐在 KEAP1 琥珀酰化和 Nrf2 信号中的作用。
Cancer Cell. 2011 Oct 18;20(4):524-37. doi: 10.1016/j.ccr.2011.09.006.
2
An antioxidant response phenotype shared between hereditary and sporadic type 2 papillary renal cell carcinoma.遗传性和散发性 2 型乳头状肾细胞癌之间存在抗氧化反应表型。
Cancer Cell. 2011 Oct 18;20(4):511-23. doi: 10.1016/j.ccr.2011.08.024.
3
Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase.血红素加氧酶与肿瘤抑制因子延胡索酸水合酶联合具有合成致死性。
Nature. 2011 Aug 17;477(7363):225-8. doi: 10.1038/nature10363.
4
Aberrant succination of proteins in fumarate hydratase-deficient mice and HLRCC patients is a robust biomarker of mutation status.琥珀酰化蛋白在富马酸水合酶缺陷型小鼠和 HLRCC 患者中的异常是突变状态的一个强有力的生物标志物。
J Pathol. 2011 Sep;225(1):4-11. doi: 10.1002/path.2932. Epub 2011 Jun 1.
5
Exploring a glycolytic inhibitor for the treatment of an FH-deficient type-2 papillary RCC.探索一种糖酵解抑制剂用于 FH 缺陷型 2 型乳头状 RCC 的治疗。
Nat Rev Urol. 2011 Mar;8(3):165-71. doi: 10.1038/nrurol.2010.234. Epub 2011 Feb 8.
6
Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution.Keap1-Nrf2 通路在应激反应和癌症演化中的分子机制。
Genes Cells. 2011 Feb;16(2):123-40. doi: 10.1111/j.1365-2443.2010.01473.x.
7
Cancer chemoprevention mechanisms mediated through the Keap1-Nrf2 pathway.癌症化学预防机制通过 Keap1-Nrf2 通路介导。
Antioxid Redox Signal. 2010 Dec 1;13(11):1713-48. doi: 10.1089/ars.2010.3221. Epub 2010 Aug 14.
8
Keap1 is a forked-stem dimer structure with two large spheres enclosing the intervening, double glycine repeat, and C-terminal domains.Keap1 是一个分叉茎二聚体结构，两个大球包含中间的双甘氨酸重复和 C 末端结构域。
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):2842-7. doi: 10.1073/pnas.0914036107. Epub 2010 Jan 27.
9
Structures of SPOP-substrate complexes: insights into molecular architectures of BTB-Cul3 ubiquitin ligases.SPOP-底物复合物的结构：对BTB-Cul3泛素连接酶分子结构的见解
Mol Cell. 2009 Oct 9;36(1):39-50. doi: 10.1016/j.molcel.2009.09.022.
10
Germline mutations in FH predispose to dominantly inherited uterine fibroids, skin leiomyomata and papillary renal cell cancer.FH基因的种系突变易导致显性遗传的子宫肌瘤、皮肤平滑肌瘤和乳头状肾细胞癌。
Nat Genet. 2002 Apr;30(4):406-10. doi: 10.1038/ng849. Epub 2002 Feb 25.
Zotero 插件