启动子结合转录因子的赖氨酸甲基化及其与癌症的相关性。
Lysine methylation of promoter-bound transcription factors and relevance to cancer.
机构信息
Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
出版信息
Cell Res. 2011 Mar;21(3):375-80. doi: 10.1038/cr.2010.174. Epub 2010 Dec 14.
Abstract
p53, NFκB, STAT3, and several other transcription factors are reversibly methylated on lysine residues by enzymes that also modify histones. The methylations of NFκB and STAT3 take place when they are bound to promoters, suggesting a more general model in which the binding of inducible transcription factors to DNA helps to recruit chromatin-modification machinery, which then may modify not only histones but also the bound transcription factors. Mutations of some histone-lysine methyltransferases and demethylases are linked to cancer, and these mutations may alter the methylation not only of histones but also of transcription factors, and thus may be tumorigenic through more than one mechanism.
摘要
p53、NFκB、STAT3 和其他一些转录因子可被可逆地赖氨酸甲基化，该过程由修饰组蛋白的酶来完成。NFκB 和 STAT3 的甲基化发生在它们与启动子结合时，这表明了一个更普遍的模型，即诱导型转录因子与 DNA 的结合有助于募集染色质修饰机制，该机制随后不仅可以修饰组蛋白，还可以修饰结合的转录因子。一些组蛋白赖氨酸甲基转移酶和去甲基酶的突变与癌症有关，这些突变不仅可能改变组蛋白的甲基化，还可能改变转录因子的甲基化，因此可能通过不止一种机制致癌。
相似文献
1
Lysine methylation of promoter-bound transcription factors and relevance to cancer.启动子结合转录因子的赖氨酸甲基化及其与癌症的相关性。
Cell Res. 2011 Mar;21(3):375-80. doi: 10.1038/cr.2010.174. Epub 2010 Dec 14.
2
Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes.组蛋白修饰酶可逆地甲基化结合在启动子上的 STAT3。
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21499-504. doi: 10.1073/pnas.1016147107. Epub 2010 Nov 23.
3
Critical roles of non-histone protein lysine methylation in human tumorigenesis.赖氨酸甲基化在人类肿瘤发生中的关键作用。
Nat Rev Cancer. 2015 Feb;15(2):110-24. doi: 10.1038/nrc3884.
4
NF-κB: Regulation by Methylation.核因子κB：甲基化调控
Cancer Res. 2015 Sep 15;75(18):3692-5. doi: 10.1158/0008-5472.CAN-15-1022. Epub 2015 Sep 3.
5
STAT3-driven transcription depends upon the dimethylation of K49 by EZH2.信号转导及转录激活因子3（STAT3）驱动的转录依赖于EZH2对K49的二甲基化作用。
Proc Natl Acad Sci U S A. 2015 Mar 31;112(13):3985-90. doi: 10.1073/pnas.1503152112. Epub 2015 Mar 12.
6
Targeting histone lysine methylation in cancer.靶向癌症中的组蛋白赖氨酸甲基化。
Pharmacol Ther. 2015 Jun;150:1-22. doi: 10.1016/j.pharmthera.2015.01.002. Epub 2015 Jan 9.
7
Negative regulation of NF-kappaB action by Set9-mediated lysine methylation of the RelA subunit.Set9介导RelA亚基赖氨酸甲基化对核因子κB活性的负调控。
EMBO J. 2009 Apr 22;28(8):1055-66. doi: 10.1038/emboj.2009.55. Epub 2009 Mar 5.
8
Oncoepigenomics: making histone lysine methylation count.肿瘤表观基因组学：让组蛋白赖氨酸甲基化发挥作用。
Eur J Med Chem. 2012 Oct;56:179-94. doi: 10.1016/j.ejmech.2012.08.010. Epub 2012 Aug 11.
9
Molecular basis for substrate recognition by lysine methyltransferases and demethylases.赖氨酸甲基转移酶和去甲基酶识别底物的分子基础。
Biochim Biophys Acta. 2014 Dec;1839(12):1404-15. doi: 10.1016/j.bbagrm.2014.06.008. Epub 2014 Jun 17.
10
Current perspectives on histone demethylases.组蛋白去甲基化酶的当前观点。
Acta Biochim Biophys Sin (Shanghai). 2007 Feb;39(2):81-8. doi: 10.1111/j.1745-7270.2007.00272.x.
引用本文的文献
1
SETD7 Dual Role in Disease and Opportunities for Therapeutic Intervention: Current Perspectives.SETD7在疾病中的双重作用及治疗干预机会：当前观点
J Inflamm Res. 2025 Sep 4;18:12191-12225. doi: 10.2147/JIR.S534623. eCollection 2025.
2
Gut microbes and their metabolites in relation to the classic tumor suppressor gene P53: a novel narrative.肠道微生物及其代谢产物与经典肿瘤抑制基因P53的关系：一种新的叙述
NPJ Biofilms Microbiomes. 2025 Jul 17;11(1):135. doi: 10.1038/s41522-025-00775-x.
3
Tailoring a novel colorectal cancer stem cell-targeted therapy by inhibiting the SMYD3/c-MYC axis.通过抑制SMYD3/c-MYC轴定制一种新型的结直肠癌干细胞靶向治疗方法。
Signal Transduct Target Ther. 2025 Jun 30;10(1):206. doi: 10.1038/s41392-025-02290-z.
4
Orthogonal Translation for Site-Specific Installation of Post-translational Modifications.用于翻译后修饰的定点安装的正交翻译。
Chem Rev. 2024 Mar 13;124(5):2805-2838. doi: 10.1021/acs.chemrev.3c00850. Epub 2024 Feb 19.
5
SETD7 Expression Is Associated with Breast Cancer Survival Outcomes for Specific Molecular Subtypes: A Systematic Analysis of Publicly Available Datasets.SETD7表达与特定分子亚型的乳腺癌生存结果相关：对公开可用数据集的系统分析
Cancers (Basel). 2022 Dec 7;14(24):6029. doi: 10.3390/cancers14246029.
6
EZH2 T367 phosphorylation activates p38 signaling through lysine methylation to promote breast cancer progression.EZH2 T367位点磷酸化通过赖氨酸甲基化激活p38信号通路，以促进乳腺癌进展。
iScience. 2022 Aug 2;25(8):104827. doi: 10.1016/j.isci.2022.104827. eCollection 2022 Aug 19.
7
EZH2-induced lysine K362 methylation enhances TMPRSS2-ERG oncogenic activity in prostate cancer.EZH2 诱导的赖氨酸 K362 甲基化增强前列腺癌中的 TMPRSS2-ERG 致癌活性。
Nat Commun. 2021 Jul 6;12(1):4147. doi: 10.1038/s41467-021-24380-6.
8
Migration and Adhesion of B-Lymphocytes to Specific Microenvironments in Mantle Cell Lymphoma: Interplay between Signaling Pathways and the Epigenetic Landscape.套细胞淋巴瘤中 B 淋巴细胞向特定微环境的迁移和黏附：信号通路与表观遗传景观的相互作用。
Int J Mol Sci. 2021 Jun 10;22(12):6247. doi: 10.3390/ijms22126247.
9
The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics.靶向乙酰化介导的基因调控在设计新的作用机制工具和潜在治疗方法中的生物学意义。
Biomolecules. 2021 Mar 18;11(3):455. doi: 10.3390/biom11030455.
10
miR‑124‑3p regulates angiogenesis in peripheral arterial disease by targeting STAT3.miR-124-3p 通过靶向 STAT3 调节外周动脉疾病中的血管生成。
Mol Med Rep. 2020 Dec;22(6):4890-4898. doi: 10.3892/mmr.2020.11538. Epub 2020 Sep 25.
本文引用的文献
1
Lysine methylation of the NF-κB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-κB signaling.SETD6 通过组蛋白甲基转移酶 GLP 将 NF-κB 亚基 RelA 的赖氨酸甲基化，将组蛋白甲基转移酶 GLP 的活性与 NF-κB 信号的持续抑制偶联。
Nat Immunol. 2011 Jan;12(1):29-36. doi: 10.1038/ni.1968. Epub 2010 Dec 5.
2
Reversible methylation of promoter-bound STAT3 by histone-modifying enzymes.组蛋白修饰酶可逆地甲基化结合在启动子上的 STAT3。
Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21499-504. doi: 10.1073/pnas.1016147107. Epub 2010 Nov 23.
3
Regulation of the androgen receptor by SET9-mediated methylation.SET9 介导的甲基化调控雄激素受体。
Nucleic Acids Res. 2011 Mar;39(4):1266-79. doi: 10.1093/nar/gkq861. Epub 2010 Oct 19.
4
Methylation of the retinoblastoma tumor suppressor by SMYD2.SMYD2 对视网膜母细胞瘤肿瘤抑制因子的甲基化。
J Biol Chem. 2010 Nov 26;285(48):37733-40. doi: 10.1074/jbc.M110.137612. Epub 2010 Sep 24.
5
Lysine methylation regulates E2F1-induced cell death.赖氨酸甲基化调控 E2F1 诱导的细胞死亡。
Mol Cell. 2010 Jul 9;39(1):152-60. doi: 10.1016/j.molcel.2010.06.006.
6
Negative regulation of hypoxic responses via induced Reptin methylation.通过诱导 Reptin 甲基化来负调控低氧反应。
Mol Cell. 2010 Jul 9;39(1):71-85. doi: 10.1016/j.molcel.2010.06.008.
7
Somatic mutations of the histone methyltransferase gene EZH2 in myelodysplastic syndromes.骨髓增生异常综合征中组蛋白甲基转移酶基因 EZH2 的体细胞突变。
Nat Genet. 2010 Aug;42(8):665-7. doi: 10.1038/ng.620. Epub 2010 Jul 4.
8
Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders.在髓系疾病中，组蛋白甲基转移酶基因 EZH2 的失活突变。
Nat Genet. 2010 Aug;42(8):722-6. doi: 10.1038/ng.621. Epub 2010 Jul 4.
9
Nonhistone protein acetylation as cancer therapy targets.非组蛋白蛋白乙酰化作为癌症治疗靶点。
Expert Rev Anticancer Ther. 2010 Jun;10(6):935-54. doi: 10.1586/era.10.62.
10
Use of forward genetics to discover novel regulators of NF-kappaB.利用正向遗传学发现 NF-κB 的新型调控因子。
Cold Spring Harb Perspect Biol. 2010 Jun;2(6):a001966. doi: 10.1101/cshperspect.a001966. Epub 2009 Dec 23.
Zotero 插件