首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >MYC oncogene involved in a t(8;22) chromosome translocation is not altered in its putative regulatory regions.
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MYC oncogene involved in a t(8;22) chromosome translocation is not altered in its putative regulatory regions.

机译:参与t(8; 22)染色体易位的MYC癌基因在其假定的调控区域未发生改变。

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摘要

We have cloned the translocation-associated MYC gene from the Burkitt lymphoma cell line (BL2) with a t(8;22) chromosomal translocation and have determined the nucleotide sequence of the first exon and of the 3' and 5' flanking regions, where sequences with putative regulatory functions have been identified. The nucleotide sequence of the 5' flanking region, which contains regions of DNase hypersensitivity and binding sites for putative regulatory proteins, is the same as that of the normal MYC. Accordingly, mutations in these regulatory regions are not required for the transcriptional deregulation of MYC in the BL2 cell line. The nucleotide sequence of the first exon is similar to that of the normal MYC [Gazin, C., Dupont de Direchin, S., Hampe, A., Masson, J. M., Martin, P., Stehelin, D. & Galibert, F. (1984) EMBO J. 3, 383-387] and has the coding capacity for a 188-residue polypeptide. However, six nucleotide changes that occur in the middle of this reading frame could result in amino acid substitutions. We also have cloned and sequenced the t(8;22) chromosomal breakpoint that is located 10 kilobases 3' of the MYC exon 3 and near the C lambda 3 gene on chromosome 22. Sequences with homology to immunoglobulin joining signals occur close to the breakpoint both on chromosome 8 and 22, providing further evidence that the immunoglobulin joining enzymes may be involved in the recombinations associated with a variety of chromosomal translocations in B and T cells.
机译:我们已经从带有at(8; 22)染色体易位的Burkitt淋巴瘤细胞系(BL2)中克隆了与易位相关的MYC基因,并确定了第一个外显子以及3'和5'侧翼区域的核苷酸序列,具有公认的监管功能。 5'侧翼区域的核苷酸序列与正常MYC的核苷酸序列相同,该核苷酸序列包含DNase超敏区域和推定调节蛋白的结合位点。因此,在BL2细胞系中MYC的转录去调节不需要这些调节区域中的突变。第一个外显子的核苷酸序列与正常MYC的核苷酸序列相似[Gazin,C.,Dupont de Direchin,S.,Hampe,A.,Masson,JM,Martin,P.,Stehelin,D.&Galibert,F (1984)EMBO J.3,383-387],并且具有188个残基多肽的编码能力。但是,在此阅读框中间发生的六个核苷酸变化可能导致氨基酸取代。我们还克隆了t(8; 22)染色体断裂点并对其进行了测序,该断裂点位于MYC外显子3的10'碱基3'处,并位于22号染色体上的C lambda 3基因附近。两者均位于8号和22号染色体上,这提供了进一步的证据,证明免疫球蛋白连接酶可能参与了与B细胞和T细胞中各种染色体易位相关的重组。

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