Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21
Cloning and genomic organization of beclin 1, a candidate tumor suppressor gene on chromosome 17q21
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DOI：
10.1006/geno.1999.5851
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发表时间：
1999-07-01
期刊：
影响因子：
4.4
通讯作者：
Levine, B
中科院分区：
文献类型：
--
作者：
Aita, VM;Liang, XH;Levine, B
Beclin 1（BECN 1）基因编码一个60 kDa的卷曲螺旋蛋白，与原型凋亡抑制剂Bcl-2相互作用。先前的研究表明，beclin 1定位于染色体17 q21上BRCA 1着丝粒的约150 kb区域，该区域通常在乳腺癌、卵巢癌和前列腺癌中缺失。Beclin 1基因全长cDNA序列编码2098 bp的转录本，包括120 bp的5'非翻译区、1353 bp的编码区和625 bp的3'非翻译区。对人类基因组PAC文库的杂交筛选鉴定出PAC 452 O 8，其含有完整的beclin 1基因。Beclin I的外显子-内含子结构的测定揭示了12个外显子，范围从61到794 bp，延伸超过12 kb的人类基因组。以PAC 452 O 8为探针，对人乳腺癌细胞系进行FISH分析，发现22个细胞系中有9个存在等位基因beclin 1缺失。对这些细胞系中的10个细胞系的基因组DNA进行测序，发现编码区或剪接点没有突变。此外，11个细胞系的北方印迹分析未发现beclin 1转录物的任何异常。这些结果表明，人乳腺癌细胞系经常含有beclin 1的等位基因缺失，但没有beclin 1编码突变。(C)北京：科学出版社.
The beclin 1 (BECN1) gene encodes a 60-kDa coiled-coil protein that interacts with the prototypic apoptosis inhibitor Bcl-2. Previous studies indicate that beclin 1 maps to a region approximately 150 kb centromeric to BRCA1 on chromosome 17q21 that is commonly deleted in breast, ovarian, and prostate cancer. The complete cDNA sequence of beclin 1 encodes a 2098-bp transcript, with a 120-bp 5' UTR, 1353-bp coding region, and 625-bp 3' UTR. Hybridization screening of a human genomic PAC library identified PAC 452O8, which contains the complete beclin 1 gene. Determination of the exon-intron structure of beclin I reveals 12 exons, ranging from 61 to 794 bp, which extend over 12 kb of the human genome. FISH analysis of human breast carcinoma cell lines using PAC 452O8 as probe identified allelic beclin 1 deletions in 9 of 22 cell lines. Sequencing of genomic DNA from 10 of these cell lines revealed no mutations in coding regions or splice junctions. Additionally, Northern blot analysis of 11 cell lines did not identify any abnormalities in beclin 1 transcripts. These results indicate that human breast carcinoma cell lines frequently contain allelic deletions of beclin 1, but not beclin 1 coding mutations. (C) 1999 Academic Press.