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通过插入莫洛尼鼠白血病病毒样DNA序列使p53基因表达失活。

Inactivation of p53 gene expression by an insertion of Moloney murine leukemia virus-like DNA sequences.

作者信息

Wolf D, Rotter V

出版信息

Mol Cell Biol. 1984 Jul;4(7):1402-10. doi: 10.1128/mcb.4.7.1402-1410.1984.

DOI:10.1128/mcb.4.7.1402-1410.1984
PMID:6095069
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC368923/
Abstract

Analysis of Abelson murine leukemia virus-transformed L12 cells which lack the p53 cellular encoded tumor antigen revealed alterations in the p53-specific genomic DNA sequences. The active p53 gene, usually contained in a 16-kilobase EcoRI DNA fragment of p53 producer cells, went through major alterations leading to the appearance of a substantially larger 28.0-kilobase p53-specific EcoRI fragment. Detailed restriction enzyme analysis, with genomic probes spanning throughout the whole active p53 gene, indicated that the L12 p53 altered gene contains all the exons and principal introns of the normal p53 16.0-kilobase gene. However, its structure was interrupted by the integration of a novel DNA segment into the noncoding intervening sequences of the first p53 intron. Analysis of the inserted sequences revealed close homology to Moloney murine leukemia virus. This Moloney leukemia murine virus-like particle resides in a 5' to 3' transcriptional orientation, similar to the p53 gene, permitting the transcription of aberrant fused mRNA molecules detected in these cells.

摘要

对缺乏p53细胞编码肿瘤抗原的阿贝尔逊鼠白血病病毒转化的L12细胞进行分析,发现p53特异性基因组DNA序列发生了改变。通常包含在p53产生细胞的16千碱基埃可里核酸酶I DNA片段中的活性p53基因发生了重大改变,导致出现了一个大得多的28.0千碱基p53特异性埃可里核酸酶I片段。使用跨越整个活性p53基因的基因组探针进行详细的限制性酶分析表明,L12 p53改变基因包含正常p53 16.0千碱基基因的所有外显子和主要内含子。然而,其结构因一个新的DNA片段整合到第一个p53内含子的非编码间隔序列中而中断。对插入序列的分析显示与莫洛尼鼠白血病病毒有密切同源性。这种莫洛尼白血病鼠病毒样颗粒以5'到3'的转录方向存在,与p53基因相似,使得在这些细胞中检测到异常融合mRNA分子的转录。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0271/368923/439d0e1d42d9/molcellb00149-0224-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0271/368923/32a3beb3e68b/molcellb00149-0221-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0271/368923/a5b85c054e61/molcellb00149-0221-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0271/368923/439d0e1d42d9/molcellb00149-0224-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0271/368923/32a3beb3e68b/molcellb00149-0221-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0271/368923/a5b85c054e61/molcellb00149-0221-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0271/368923/439d0e1d42d9/molcellb00149-0224-a.jpg

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