Isaac F López-Moyado, Myunggon Ko, Patrick G Hogan, Anjana Rao
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引用次数: 0
摘要
十-十一转位(TET)蛋白是一种铁依赖型和α-酮戊二酸依赖型二氧 化酶,能依次将 5-甲基胞嘧啶(5mC)的甲基氧化成 5-羟甲基胞嘧啶(5hmC)、5-甲酰基胞嘧啶(5fC)和 5-羧基胞嘧啶(5caC)。这三种表观遗传修饰都是 DNA 去甲基化的中间产物。TET 蛋白受转录因子和 RNA 聚合酶 II 的招募,对增强子和基因体上的 5mC 进行修饰,从而在发育、细胞系分化和细胞活化过程中调节基因表达。然而,目前还不清楚 TET 酶氧化 5mC 和介导 DNA 去甲基化的既定生化活动与已知的 TET 缺乏症与炎症、克隆造血和癌症之间的关系。有迹象表明,TET 缺乏症以信号依赖方式促进细胞增殖的能力可用于癌症免疫疗法。在这篇综述中,我们借鉴了最近在免疫系统细胞中的发现,以说明 TET 蛋白如何影响细胞功能的既有观点和新观点。免疫学年刊》(Annual Review of Immunology)第 42 卷的最终在线出版日期预计为 2024 年 4 月。修订后的预计日期请参见 http://www.annualreviews.org/page/journal/pubdates。
TET Enzymes in the Immune System: From DNA Demethylation to Immunotherapy, Inflammation, and Cancer.
Ten-eleven translocation (TET) proteins are iron-dependent and α-ketoglutarate-dependent dioxygenases that sequentially oxidize the methyl group of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). All three epigenetic modifications are intermediates in DNA demethylation. TET proteins are recruited by transcription factors and by RNA polymerase II to modify 5mC at enhancers and gene bodies, thereby regulating gene expression during development, cell lineage specification, and cell activation. It is not yet clear, however, how the established biochemical activities of TET enzymes in oxidizing 5mC and mediating DNA demethylation relate to the known association of TET deficiency with inflammation, clonal hematopoiesis, and cancer. There are hints that the ability of TET deficiency to promote cell proliferation in a signal-dependent manner may be harnessed for cancer immunotherapy. In this review, we draw upon recent findings in cells of the immune system to illustrate established as well as emerging ideas of how TET proteins influence cellular function.
期刊介绍:
The Annual Review of Immunology, in publication since 1983, focuses on basic immune mechanisms and molecular basis of immune diseases in humans. Topics include innate and adaptive immunity; immune cell development and differentiation; immune control of pathogens (viruses, bacteria, parasites) and cancer; and human immunodeficiency and autoimmune diseases. The current volume of this journal has been converted from gated to open access through Annual Reviews' Subscribe to Open program, with all articles published under a CC BY license.