The enhancer of human papillomavirus type 16: binding sites for the ubiquitous transcription factors oct-1, NFA, TEF-2, NF1, and AP-1 participate in epithelial cell-specific transcription
The enhancer of human papillomavirus type 16: binding sites for the ubiquitous transcription factors oct-1, NFA, TEF-2, NF1, and AP-1 participate in epithelial cell-specific transcription
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人乳头瘤病毒16型增强子：普遍存在的转录因子oct-1、NFA、TEF-2、NF1和AP-1的结合位点参与上皮细胞特异性转录
作者：
T. Chong;Doris Apt;Bernd Gloss;Merlina Isa;Hans
人乳头瘤病毒16型增强子(HPV-16)被认为是上皮细胞，特别是宫颈癌来源的细胞系所特有的。我们用完全增强子和不重叠的亚克隆重新检验了这一假说，发现所有克隆在来自表皮和宫颈癌、乳腺癌和结肠癌的上皮细胞系中都是活跃的，但在成纤维细胞、淋巴瘤和胚胎癌细胞中不活跃。虽然病毒只感染人的粘膜上皮细胞，但增强子的活性与转基因上皮细胞的确切类型或起源种类无关。尽管有上皮细胞的特异性，我们发现HPV-16增强子的活性与巨细胞病毒增强子和猿猴病毒40增强子的活性有很大的不同，这与细胞系有关。这表明增强子元件的不同数量贡献，而不是全有或全无开关的调控。细胞类型特异性由400bp增强子的91bp亚克隆维持。该片段的大部分增强子活性被普遍存在的因子AP-1、核因子1(NF1)或TEF-2的结合位点的交替突变所消除。这三种类型的因素在没有合作的情况下结合了这个91bp的增强子，尽管激活似乎是协同的。在91bp的片段之外，乳头瘤病毒增强子的一个典型基序，即侧翼有NF1结合位点的八聚体序列，有助于增强功能，因为它的活性在缺失后显著降低。在HPV-16中，这个基序被Oct-1因子以及一个可能是新的因子NFA结合，而HPV-11的一个相关基序只被NFA识别。经检测，参与HPV增强子激活的五种转录因子中没有一种仅限于上皮细胞，但NF1、AP-1和OCT-1在HeLa细胞中的浓度高于成纤维细胞。只有NF1表现出一些定性的细胞类型特异性差异。我们认为HPV-16增强子的上皮特异性是通过与假定普遍存在的转录因子的结合位点来实现的。这种激活的机制显然涉及不同浓度的因子之间的协同作用，并可能包括存在于这些因子的DNA结合域之外的特定细胞功能差异。
The enhancer of human papillomavirus type 16 (HPV-16) is considered to be specific for epithelial cells, in particular for cervical carcinoma-derived cell lines. We reexamined this hypothesis with the complete enhancer as well as nonoverlapping subclones and found all clones to be active in epithelial cell lines derived from the epidermis and from carcinomas of the cervix, mammary gland, and colon, but inactive in fibroblast, lymphoma, and embryonal carcinoma cells. Although the virus infects only human mucosal epithelia, enhancer activity was independent of the exact type or of the species of origin of the transfected epithelial cell. In spite of epithelial cell specificity, we found that the activity of the HPV-16 enhancer varied strongly from a cytomegalovirus enhancer and the simian virus 40 enhancer in a cell line-dependent manner. This suggests varying quantitative contributions of enhancer elements rather than regulation by an all-or-none switch. Cell type specificity was maintained by a 91-bp subclone of the 400-bp enhancer. Most of the enhancer activity of this fragment was eliminated by alternative mutations in binding sites for the ubiquitous factors AP-1, nuclear factor 1 (NF1), or TEF-2. These three types of factors bind this 91-bp enhancer without cooperation, although activation appears to be synergistic. Outside the 91-bp fragment, a motif typical for papillomavirus enhancers, namely an octamerlike sequence flanked by an NF1-binding site, contributes to enhancer function, as the activity was strongly reduced upon its deletion. In HPV-16, this motif is bound by the oct-1 factor as well as by a probably novel factor, NFA, whereas a related motif of HPV-11 is recognized only by NFA. On examination, none of the five types of transcription factors involved in HPV enhancer activation was restricted to epithelial cells, but NF1, AP-1, and oct-1 were present in higher concentration in HeLa cells than in fibroblasts. Only NF1 showed some qualitative cell type-specific differences. We propose that the epithelial specificity of the HPV-16 enhancer is brought about via binding sites for supposed ubiquitous transcription factors. The mechanism of this activation apparently involves synergism between factors that vary in concentration and may include cell-specific functional differences residing outside the DNA-binding domain of these factors.
影响因子：
56.9
作者：
DYSON, N;HOWLEY, PM;HARLOW, E
通讯作者：
HARLOW, E
通过含有不同细胞依赖性和 AP-1 响应模块的 88 核苷酸增强子对人乳头瘤病毒 16 P97 启动子进行转录激活。
DOI：
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发表时间：
1990
期刊：
The New biologist
影响因子：
--
作者：
Cripe,TP;Alderborn,A;Anderson,RD;Parkkinen,S;Bergman,P;Haugen,TH;Pettersson,U;Turek,LP
通讯作者：
Turek,LP