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SETD2是哺乳动物中唯一的组蛋白H3K36的特异性三甲基转移酶,它的编码基因位于第三号染色体的3p21.31区域。SETD2蛋白是一个230 k D、含有SET结构域的蛋白,最早是由人造血干细胞分离的,也被认为是与亨廷顿病的发病机制相关。它是生物转录延伸过程中的重要组成部分,能够与RNA聚合酶Ⅱ的最大亚基Rbp1结合,参与基因的转录延伸。SETD2还能通过编码区的去乙酰化抑制转录起始的频率以保证基因转录的高保真度,从而预防肿瘤的发生;同时SETD2也能激活转录因子p53及下游凋亡靶基因发挥抑癌作用。SETD2在DNA修复方面也具有重要作用,它是人错配基因修复和人同源基因修复过程中不可缺少的重要部分。已经有研究表明在多种肿瘤中SETD2均发生了突变,包括肾透明细胞癌、小儿晚期神经胶质瘤、急性T淋巴细胞白血病等,对某些特定肿瘤的分期和预后也有显著影响。本文将介绍SETD2在人体内的多种功能,并对其在肿瘤发生发展中的作用机制进行综述。
SETD2 is the only histone H3K36-specific trimethyltransferase in mammals whose coding gene is located on the 3p21.31 region on chromosome 3. The SETD2 protein, a 230 kD SET domain-containing protein, was first isolated from human hematopoietic stem cells and is also thought to be involved in the pathogenesis of Huntington’s disease. It is an important part of the process of biological transcription elongation, which can bind to Rbp1, the largest subunit of RNA polymerase II, and participate in the transcriptional extension of the gene. SETD2 can also inhibit the frequency of transcriptional initiation by deacetylating the coding region to ensure the high fidelity of gene transcription so as to prevent the occurrence of the tumor. SETD2 can also activate the transcription factor p53 and the downstream target genes to exert anti-tumor effect. SETD2 also plays an important role in DNA repair, which is an integral part of human mismatch repair and human homologous gene repair. Studies have shown that SETD2 mutations have occurred in many tumors, including renal clear cell carcinoma, pediatric advanced glioma, acute lymphoblastic leukemia, etc., also have a significant impact on the staging and prognosis of some specific tumors. This article will introduce SETD2 in the human body a variety of functions, and its mechanism in tumor development and review.