Revelations of a captive: retroviral Qin and the oncogenicity of winged helix proteins.
Revelations of a captive: retroviral Qin and the oncogenicity of winged helix proteins.
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俘虏的启示：逆转录病毒Qin和翼螺旋蛋白的致癌性。
DOI：
10.1006/viro.1997.8846
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发表时间：
1997
期刊：
影响因子：
3.7
通讯作者：
Freyaldenhoven,BS
中科院分区：
文献类型：
--
作者：
Vogt,PK;Li,J;Freyaldenhoven,BS
从逆转录病毒到细胞癌基因的途径是一个分叉（fkh），指的是突变体的表型。所有逆转录病毒癌基因都来源于宿主细胞前基因组和后基因组中的同源异型转化。它们是突变的，并且类似于肠，在病毒基因组的两端具有头状结构。它们的复制、表达、胚胎（Weigel等，1989年）。肝细胞核因子3b（hepatocyte nuclear factor 3b，HNF-3b）是病毒控制下的一种细胞因子（综述见Bishop，1983; Varmus，1984）。作为遗传学-在哺乳动物中鉴定的第一种WH蛋白（Lai等人，cally改变俘虏，他们揭示了潜在的属性，1991年）。它在结、脊索、底板中高表达，在其细胞祖细胞中不明显。小鼠胚胎qin基因板和内胚层。HNF-3b无效是最近的例子，发现作为细胞来源的肿瘤突变导致胚胎死亡，具有结节遗传决定簇禽肉瘤病毒31（ASV 31）（Li和脊索形成（Ang和Rossant，1994;和沃格特，1993）中的缺陷。ASV 31的基因组与Weinstein等人的基因组相似，1994年）。其他缺陷型转化逆转录病毒的六个以上WH基因（图1）。现在已经通过种系敲除分析了部分，并且所有的病毒gag和所有的pol区域都缺失，并且这些显示了信息表型（Ang和Rossant，被表达为Gag- 1994的qin插入物替代; Dou等人，1997; Hatini等人，1996; Labosky等人，Qin融合蛋白。qin或gag-qin序列ex- 1997; Weinstein等人，1994; Winnier等人，1997; Xuan从ASV 31基因组中切下并插入到等，1995年）。一个非常熟悉的发育性逆转录病毒表达载体RCAS的例子显示，相同的肿瘤重要性WH基因是裸鼠，其免疫原性潜力与天然ASV 31相同。因此，qin功能缺陷和毛发缺乏是由作为ASV 31的致癌决定子的突变引起的;它是编码WH转录致癌基因的whn基因中的作用（Chang等人，1996; Li和沃格特，1993）。因子（Nehls等人，1994年）。Qin编码一种蛋白质，属于有翼Qin，是哺乳动物脑因子1螺旋转录因子家族的同源物。这一点的标志（BF-1）。BF-1的表达局限于端粒家族，是一个保守的DNA结合结构域，长度约为100个脑、视网膜的鼻侧半部和视柄氨基酸（Lai等人，1993; Kaufmann and（Tao and Lai，1992）.在发育中的鸡胚胎中，Knöchel，1996年）。Qin的该结构域表达中的三个α螺旋之一也局限于端脑，与双-（Chang等人，1995年）。具有BF-1无效突变的小鼠死亡。这些接触通过出生时相邻的环结构的发育中的严重缺陷而稳定，所述环结构也与DNA相互作用，因此是大脑半球（Xuan等人，1995年）。BF-1被认为是术语“有翼螺旋”（WH）（Brennan，1993; Clark等人，来控制皮质祖细胞的复制，但1993年）。在DNA结合结构域之外，WH蛋白的这种调节机制尚不清楚，显示出相当大的序列和结构多样性。（McConnell，1995年）。Qin在视网膜中的过表达--它们在发育中的鸟类视网膜中作为一种重要的器官传递载体的决定子发挥作用，从而扭曲了视觉表达和组织分化（Costa，1994）。在视顶盖上的投影图，可能是由编码WH蛋白的非原型基因干扰了正常细胞的发育。
The path from retrovirus to cellular oncogene is a com- forkhead (fkh), refers to the phenotype of mutants that mon one. All retroviral oncogenes are derived from the show homeotic transformations in the anterior and postegenome of the host cell. They are mutated and assimi- rior gut with head-like structures at both ends of the lated into the viral genome. Their replication, expression, embryo (Weigel et al., 1989). The developmental regulaand movement into new cells are all under viral control tor hepatocyte nuclear factor 3b (HNF-3b) was one of (for reviews see Bishop, 1983; Varmus, 1984). As geneti- the first WH proteins identified in mammals (Lai et al., cally altered captives, they reveal latent properties that 1991). It is highly expressed in the node, notochord, floor are not evident in their cellular progenitors. The qin gene plate, and endoderm of the mouse embryo. HNF-3b null is a recent example, discovered as a cell-derived onco- mutations cause embryonic lethality with defects in node genicdeterminantinaviansarcomavirus31 (ASV31)(Li and notochord formation (Ang and Rossant, 1994; and Vogt, 1993). The genome of ASV 31 is similar to that Weinstein et al., 1994). More than half a dozen WH genes of other defective transforming retroviruses (Fig. 1). Part have now been analyzed by germ line knockouts, and all of the viral gag and all of the pol region are missing and of these show informative phenotypes (Ang and Rossant, replaced by the qin insert that is expressed as a Gag– 1994; Dou et al., 1997; Hatini et al., 1996; Labosky et al., Qin fusion protein. The qin or gag–qin sequences ex- 1997; Weinstein et al., 1994; Winnier et al., 1997; Xuan cised from the ASV 31 genome and inserted into the et al., 1995). A very familiar example of a developmentally retroviral expression vector RCAS show the same onco- important WH gene is the nude mouse, whose immunogenic potential as the native ASV 31. Therefore, qin func- logical deficiencies and lack of hair result from a mutations as the oncogenic determinant of ASV 31; it is its tion in the whn gene that codes for a WH transcription oncogene (Chang et al., 1996; Li and Vogt, 1993). factor (Nehls et al., 1994). Qin codes for a protein that belongs to the winged Qin is the homolog of the mammalian brain factor 1 helix family of transcription factors. The hallmark of this(BF-1). The expression of BF-1 is restricted to the telenfamily is a conserved DNA binding domain, about 100 cephalon, the nasal half of the retina, and the optic stalk amino acids in length (Lai et al., 1993; Kaufmann and(Tao and Lai, 1992). In the developing chicken embryo Knöchel, 1996). One of the three a helixes in this domain expression of Qin is also confined to the telencephalon makes contacts with the major groove of double-(Chang et al., 1995). Mice with null mutations of BF-1 die stranded DNA. These contacts are stabilized by adjacent at birth with severe defects in the development of the loop structures that also interact with the DNA, hence cerebral hemispheres (Xuan et al., 1995). BF-1 is thought the term ‘‘winged helix’’(WH)(Brennan, 1993; Clark et al., to control the replication of cortical progenitor cells, but 1993). Outside the DNA binding domain, WH proteins the mechanism of this regulation is not understood show considerable diversity of sequence and structure.(McConnell, 1995). Overexpression of Qin from a retrovi-They function prominently as determinants of organ de- ral vector in the developing avian retina distorts the visual velopment and tissue differentiation (Costa, 1994). The projection map on the optic tectum, presumably by inprototype gene coding for a WH protein was discovered terfering with normal …