人类乳头瘤病毒16型E7基因编码的交换活化和转化功能类似于腺病毒E1AA的功能
W C Phelps1, C L Yee, K Münger
1Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.
Cell
|May 20, 1988
概括
人类乳头瘤病毒 (HPV) 与异位癌有关,大多数宫癌中发现HPV-16. HPV-16 E7 蛋白与腺病毒 E1A 有相似之处,具有转录性交换活化和细胞转化功能.
科学领域:
- 在瘤学瘤学.
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 临床和流行病学研究表明,人类乳头瘤病毒 (HPV) 在无遗传性恶性瘤中涉及.
- 在宫癌中,HPV-16是检测最频繁的HPV类型,超过60%.
- 在癌症中,HPV-16被积极转录,在E6和E7早期的开放阅读框架中有大量的转录.
研究的目的:
- 研究HPV-16 E7蛋白和腺病毒E1A蛋白之间的功能和结构相似性.
- 为了确定HPV-16 E7蛋白是否具有转录性交换活化和细胞转化能力.
- 为了比较HPV-16 E7的转化功能与腺病毒E1A的转化功能.
主要方法:
- 对HPV-16 E7基因产物活性进行分析.
- 使用腺病毒E2促进体的交易活化测试.
- 在初级大鼠婴儿脏细胞中使用激活的ras瘤基因进行同转化测试.
- 在已建立的小鼠细胞中进行转化试验.
- 在HPV-16 E7和腺病毒E1A保护域之间比较氨基酸序列.
主要成果:
- HPV-16 E7 开放的读取框架编码了转录的交换激活和细胞转换功能.
- HPV-16 E7 基因产物对腺病毒 E2 促进体进行了交换激活.
- HPV-16 E7与激活的ras瘤基因合作,转化初级婴儿大鼠脏细胞.
- HPV-16 E7 证明了转化已建立的小鼠细胞的能力,这种功能在腺病毒 E1A 中没有观察到.
- 在HPV-16 E7的氨基酸序列和腺病毒E1A蛋白的保存域1和2之间发现了惊人的相似之处.
结论:
- HPV-16 E7 蛋白与腺病毒 E1A 蛋白具有功能和结构上的相似性.
- 通过转录调节和细胞转化,HPV-16 E7在异位性恶性瘤的瘤发生中发挥着重要作用.
- 这些发现有助于理解HPV诱导的癌症背后的分子机制.
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