VAV, A NOVEL HUMAN ONCOGENE DERIVED FROM A LOCUS UBIQUITOUSLY EXPRESSED IN HEMATOPOIETIC-CELLS
VAV, A NOVEL HUMAN ONCOGENE DERIVED FROM A LOCUS UBIQUITOUSLY EXPRESSED IN HEMATOPOIETIC-CELLS
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DOI：
10.1002/j.1460-2075.1989.tb08354.x
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发表时间：
1989-08-01
期刊：
影响因子：
11.4
通讯作者：
BARBACID, M
中科院分区：
文献类型：
--
作者：
KATZAV, S;MARTINZANCA, D;BARBACID, M
一种新的人类癌基因，命名为vav，是在基因转移试验中通过基因重排产生的。vav癌基因指导3.0 kb mRNA的合成，我们从中分离出2.8 kb长的互补DNA拷贝。对该克隆的核苷酸序列分析表明，其5“167 bp来自于在基因转移过程中作为选择标记共转染的pSV 2neo DNA。其余2597 bp与现有数据库中的基因无关，表明vav癌基因可能来自一个新的人类基因座。vav癌基因cDNA克隆包含2391 bp长的开放阅读框（ORF），其能够指导797个氨基酸长的多肽的合成。预测的vav癌基因蛋白质序列显示出几个让人联想到转录因子的基序。它们包括一个高度酸性的氨基末端区域，由一个富含脯氨酸的序列（可能是铰链区）与两个假定的核定位信号分开。此外，我们确定了两个锌指样结构域，其中之一符合经典模式Cys-X2-Cys-X13-X2-Cys先前发现赋予反式激活腺病毒E1 A蛋白。其正常等位基因vav原癌基因的转录仅在造血来源的细胞中观察到，包括红系、淋巴系和髓系细胞。这些发现提高了这种新基因座可能在造血中发挥重要作用的可能性。
A novel human oncogene, designated vav, was generated by a genetic rearrangement during gene transfer assays. The vav oncogene directs the synthesis of a 3.0 kb mRNA from which we isolated a 2.8 kb-long complementary DNA copy. Nucleotide sequence analysis of this vav ocongene cDNA clone revealed that its 5'' 167 bp were derived from pSV2neo DNA cotransfected as a selectable marker during gene transfer. The remaining 2597 bp were unrelated to genes included in current data bankds, indicating that the vav oncogene is likely to be derived from a novel human locus. The vav oncogene cDNA clone encompasses a 2391 bp long open reading frame (ORF) capable of directing the synthesis of a 797 amino acid long polypeptide. The predicted vav oncogene protein sequence exhibits several motifs reminiscent of transcriptional factors. They include a highly acidic amino-terminal region separated from two putative nuclear localization signals by a proline-rich sequence presumably a hinge region. In addition, we identified two zinc-finger-like domains, one of which conforms to the canonical pattern Cys-X2-Cys-X13-X2-Cys previously found to confer trans-activating to the adenovirus E1A protein. Transcription of its normal allele, the vav proto-oncogene, has been exclusively observed in cells of hematopoietic origin, including those of erythroid, lymphoid and myeloid lineages. These findings raise the possibility that this novel locus might play an important role in hematopoiesis.