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禽成红细胞增多症病毒的位点特异性诱变:成纤维细胞转化不需要v-erb-A。

Site-specific mutagenesis of avian erythroblastosis virus: v-erb-A is not required for transformation of fibroblasts.

作者信息

Sealy L, Moscovici G, Moscovici C, Bishop J M

出版信息

Virology. 1983 Oct 15;130(1):179-94. doi: 10.1016/0042-6822(83)90126-5.

DOI:10.1016/0042-6822(83)90126-5
PMID:6314644
Abstract

Avian erythroblastosis virus (AEV) is an acutely transforming retrovirus whose putative oncogenes (v-erb-A and v-erb-B) encode the proteins P74gag-erb-A and P61-68erb-B. The existence of these two gene products has prompted the question of whether one or both proteins are required in the transformation of erythroblasts and fibroblasts by AEV. In the accompanying manuscript, we describe the use of site-specific mutagenesis to generate mutants of AEV unable to synthesize P61-68erb-B. Here we present our analysis of the oncogenic potential of an AEV mutant unable to synthesize P74gag-erb-A due to a large deletion encompassing both gag and v-erb-A sequences. The erb-A-mutant retrovirus propagated quite poorly on fibroblasts in culture; however, fibroblasts harboring the erb-A mutant genome were transformed in the absence of P74gag-erb-A expression. The mutant virus failed to induce erythroleukemias in chickens, but the validity of this finding is compromised by the poor replicative capacity of the mutant. The results presented in this and the preceding manuscript indicate that P61-68erb-B is both necessary and sufficient for neoplastic transformation of fibroblasts by AEV; by contrast, a role for p74gag-erb-A in leukemogenesis by AEV has not yet been rigorously excluded.

摘要

禽成红细胞增多症病毒(AEV)是一种急性转化逆转录病毒,其推定的癌基因(v-erb-A和v-erb-B)编码P74gag-erb-A和P61-68erb-B蛋白。这两种基因产物的存在引发了一个问题,即AEV转化成红细胞和成纤维细胞时,是需要其中一种蛋白还是两种蛋白都需要。在随附的论文中,我们描述了如何使用位点特异性诱变来生成无法合成P61-68erb-B的AEV突变体。在此,我们展示了对一种因大片段缺失(涵盖gag和v-erb-A序列)而无法合成P74gag-erb-A的AEV突变体致癌潜力的分析。erb-A突变逆转录病毒在培养的成纤维细胞上繁殖能力很差;然而,携带erb-A突变基因组的成纤维细胞在没有P74gag-erb-A表达的情况下也发生了转化。该突变病毒未能在鸡中诱发红细胞白血病,但由于该突变体的复制能力较差,这一发现的有效性受到了影响。本论文及前一篇论文的结果表明,P61-68erb-B对于AEV诱导成纤维细胞发生肿瘤转化既是必需的也是充分的;相比之下,尚未严格排除p74gag-erb-A在AEV诱导白血病发生过程中的作用。

相似文献

1
Site-specific mutagenesis of avian erythroblastosis virus: v-erb-A is not required for transformation of fibroblasts.禽成红细胞增多症病毒的位点特异性诱变:成纤维细胞转化不需要v-erb-A。
Virology. 1983 Oct 15;130(1):179-94. doi: 10.1016/0042-6822(83)90126-5.
2
Site-specific mutagenesis of avian erythroblastosis virus: erb-B is required for oncogenicity.禽成红细胞增多症病毒的位点特异性诱变:致癌性需要erb-B。
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Mutant of avian erythroblastosis virus defective for erythroblast transformation: deletion in the erb portion of p75 suggests function of the protein in leukemogenesis.对成红细胞转化有缺陷的禽成红细胞增多症病毒突变体:p75的erb部分缺失表明该蛋白在白血病发生中的作用。
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Subcellular localization of the v-erb-B protein, the product of a transforming gene of avian erythroblastosis virus.禽成红细胞增多症病毒转化基因产物v-erb-B蛋白的亚细胞定位。
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Mutant avian erythroblastosis virus with restricted target cell specificity.
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Transforming capacities of avian erythroblastosis virus mutants deleted in the erbA or erbB oncogenes.在erbA或erbB癌基因中缺失的禽成红细胞增多症病毒突变体的转化能力。
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Characterization of the oncogene (erb) of avian erythroblastosis virus and its cellular progenitor.禽成红细胞增多症病毒癌基因(erb)及其细胞起源的特征分析。
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Structural domains of the avian erythroblastosis virus erbB protein required for fibroblast transformation: dissection by in-frame insertional mutagenesis.禽成红细胞增多症病毒erbB蛋白诱导成纤维细胞转化所需的结构域:通过读码框内插入诱变进行剖析
J Virol. 1986 May;58(2):542-53. doi: 10.1128/JVI.58.2.542-553.1986.

引用本文的文献

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Proc Natl Acad Sci U S A. 1984 May;81(10):3000-4. doi: 10.1073/pnas.81.10.3000.
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Cellular oncogenes (c-erb-A and c-erb-B) located on different chicken chromosomes can be transduced into the same retroviral genome.
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Mol Cell Biol. 1984 Aug;4(8):1627-30. doi: 10.1128/mcb.4.8.1627-1630.1984.
4
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Proc Natl Acad Sci U S A. 1984 Aug;81(15):4874-8. doi: 10.1073/pnas.81.15.4874.
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Mutagenesis of avian carcinoma virus MH2: only one of two potential transforming genes (delta gag-myc) transforms fibroblasts.禽癌病毒MH2的诱变:两个潜在的转化基因(δgag-myc)中只有一个能转化成纤维细胞。
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