NUCLEOTIDE-SEQUENCE AND TOPOGRAPHY OF CHICKEN C-FPS - GENESIS OF A RETROVIRAL ONCOGENE ENCODING A TYROSINE-SPECIFIC PROTEIN-KINASE

NUCLEOTIDE-SEQUENCE AND TOPOGRAPHY OF CHICKEN C-FPS - GENESIS OF A RETROVIRAL ONCOGENE ENCODING A TYROSINE-SPECIFIC PROTEIN-KINASE
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DOI:
10.1016/0022-2836(85)90083-x
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发表时间:
1985-01-01
影响因子:
5.6
通讯作者:
BISHOP, JM
BISHOP, JM
中科院分区:
生物学2区
文献类型:
--
作者:
HUANG, CC;HAMMOND, C;BISHOP, JM

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分离携带细胞原癌基因c-fps部分的鸡DNA的分子克隆,然后确定与逆转录病毒癌基因v-fps相关的基因的所有区域的核苷酸序列。c-fps中v-fps的同源性存在于至少19个散布的片段上,其中17个代表完整的外显子,其中2个可能仅代表部分外显子。这些片段的融合重建了v-fps的传真。在编码酪氨酸特异性蛋白激酶活性的2个基因的结构域中,c-fps内的内含子和外显子的排列不同于相关原癌基因c-src。内含子出现在基因复制之后,产生了c-src和c-fps。揭示了2种独立分离的禽肉瘤病毒(PRCII和Fujinami株)基因组中病毒和细胞结构域之间的潜在连接。左边的连接可以很好地定义:它们出现在c-fps中的相同位置,但在病毒基因gag中的不同位置。右边的连接点不能精确定义,因为它们包括一个起源未知的10-15个核苷酸的序列。在PRCII病毒的基因组中,该序列的组成表明它来自c-fps信使RNA的多聚腺苷酸化的3“末端。如果这一推论被证明是正确的,那么这些数据将提供直接证据,证明逆转录病毒转导过程中的右侧重组发生在RNA中间体之间。不管这些模糊性,这两个路口都位于c-fps的外显子内,两者都可能是由非同源重组形成的(尽管后一种说法的证据不是决定性的)。PRCII病毒基因组中的c-fps的转导形式中缺失了1020个核苷酸的序列,显然是通过c-fps内重复的序列之间的同源重组。藤波病毒可能包含c-fps的整个编码结构域,但突变已经在该基因的病毒版本中产生了26个氨基酸取代。PRCII病毒中c-fps的部分缺失版本不包含会改变氨基酸序列的突变。
Molecular clones of chicken DNA that carry portions of the cellular proto-oncogene c-fps and then determined the nucleotide sequence of all regions of the gene that are related to the retroviral oncogene v-fps, were isolated. The homology of v-fps within c-fps resides on at least 19 interspersed segments, 17 of which represent complete exons and 2 of which may represent only portions of exons. Fusion of these segments reconstructs a facsimile of v-fps. The arrangement of introns and exons within c-fps differs from that of the related proto-oncogene c-src in the domains of the 2 genes that encode tyrosine-specific protein kinase activity. The introns arose subsequent to the gene duplication that engendered c-src and c-fps. Potential junctions between viral and cellular domains in the genomes of 2 independently isolated avian sarcoma viruses (the PRCII and Fujinami strains) were revealed. The lefthand junctions can be well defined: they occur at the same position in c-fps but at different positions in the viral gene gag. The righthand junctions cannot be defined as precisely because they include a sequence of 10-15 nucleotides whose origin is not known. In the genome of PRCII virus, the composition of this sequence suggests that it arose from the polyadenylated 3'' terminus of the c-fps messenger RNA. If this deduction proves to be correct, the data will provide direct evidence that the righthand recombination during transduction by retroviruses occurs between RNA intermediates. Irrespective of these ambiguities, both junctions are located within exons of c-fps, and both may have been formed by non homologous recombination (although the evidence for the latter statement is not decisive). A sequence of 1020 nucleotides has been deleted from the transduced version of c-fps in the genome of PRCII virus, apparently by homologous recombination between sequences repeated within c-fps. Fujinami virus may contain the entire coding domain of c-fps, but mutations have created 26 amino acid substitutions in the viral version of the gene. The partially deleted version of c-fps in PRCII virus contains no mutations that would alter the amino acid sequence.