Showe L C, Moore R C, Erikson J, Croce C M
Proc Natl Acad Sci U S A. 1987 May;84(9):2824-8. doi: 10.1073/pnas.84.9.2824.
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.
我们从具有t(8;22)染色体易位的伯基特淋巴瘤细胞系(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,在这些区域中已鉴定出具有假定调节功能的序列。5'侧翼区域的核苷酸序列与正常MYC的相同,该区域包含对DNA酶敏感的区域和假定调节蛋白的结合位点。因此,在BL2细胞系中,MYC转录失调并不需要这些调节区域发生突变。第一个外显子的核苷酸序列与正常MYC的相似[加赞,C.,杜邦·德·迪雷欣,S.,汉佩,A.,马森,J.M.,马丁,P.,斯特埃林,D.和加利贝尔,F.(1984年)《欧洲分子生物学组织杂志》3,383 - 387],并且具有编码188个氨基酸残基多肽的能力。然而,在这个阅读框中间发生的六个核苷酸变化可能导致氨基酸替换。我们还克隆并测序了位于MYC外显子3下游10千碱基处且靠近22号染色体上C lambda 3基因的t(8;22)染色体断点。在8号和22号染色体上,与免疫球蛋白连接信号具有同源性的序列靠近断点,这进一步证明免疫球蛋白连接酶可能参与了与B细胞和T细胞中多种染色体易位相关的重组。