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bcl-2的cDNA克隆及结构分析,以及由t(14;18)易位产生的bcl-2/免疫球蛋白杂交转录本

Cloning and structural analysis of cDNAs for bcl-2 and a hybrid bcl-2/immunoglobulin transcript resulting from the t(14;18) translocation.

作者信息

Cleary M L, Smith S D, Sklar J

出版信息

Cell. 1986 Oct 10;47(1):19-28. doi: 10.1016/0092-8674(86)90362-4.

DOI:10.1016/0092-8674(86)90362-4
PMID:2875799
Abstract

cDNAs for the bcl-2 mRNA were cloned from a human common acute lymphoblastic leukemia cell line. Nucleotide sequence analyses showed that the 6 kb bcl-2 mRNA potentially encodes a 26 kd protein that is homologous to a predicted Epstein-Barr virus protein. Most t(14;18) translocation breakpoints cluster within a narrow region of a 5.4 kb exon that contains a long 3'-untranslated region of the bcl-2 mRNA. As a result of t(14;18) translocation, hybrid bcl-2/immunoglobulin heavy chain transcripts are produced that consist of the 5' half of the bcl-2 mRNA fused to a "decapitated" immunoglobulin heavy chain mRNA. Nucleotide sequence analyses confirmed that the hybrid transcripts continue to encode a normal bcl-2 protein. Our results suggest that t(14;18) translocations alter expression of the bcl-2 gene both by transcriptional activation and by abnormal posttranscriptional regulation of bcl-2 mRNA.

摘要

bcl-2信使核糖核酸的互补脱氧核糖核酸是从一种人类常见急性淋巴细胞白血病细胞系中克隆出来的。核苷酸序列分析表明,6千碱基的bcl-2信使核糖核酸可能编码一种26千道尔顿的蛋白质,该蛋白质与一种预测的爱泼斯坦-巴尔病毒蛋白同源。大多数t(14;18)易位断点聚集在一个5.4千碱基外显子的狭窄区域内,该外显子包含bcl-2信使核糖核酸的一个长3'-非翻译区。由于t(14;18)易位,产生了由bcl-2信使核糖核酸的5'半部分与“无头”免疫球蛋白重链信使核糖核酸融合而成的杂合bcl-2/免疫球蛋白重链转录本。核苷酸序列分析证实,杂合转录本继续编码一种正常的bcl-2蛋白。我们的结果表明,t(14;18)易位通过转录激活和bcl-2信使核糖核酸的异常转录后调控改变bcl-2基因的表达。

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