Phelps W C, Yee C L, Münger K, Howley P M
Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.
Cell. 1988 May 20;53(4):539-47. doi: 10.1016/0092-8674(88)90570-3.
Clinical and epidemiological data have implicated the human papillomaviruses (HPVs) as having an etiologic role in some anogenital malignancies, with HPV-16 being most frequently (greater than 60%) detected in cervical carcinoma. HPV-16 is actively transcribed in the cancers; the most abundant transcripts map to the E6 and E7 early open reading frames. Evidence is presented that the HPV-16 E7 open reading frame encodes transcriptional transactivation and cellular transformation functions analogous to those of adenovirus E1A proteins. Specifically, the HPV-16 E7 gene product could transactivate the adenovirus E2 promoter and cooperate with an activated ras oncogene to transform primary baby rat kidney cells. The E7 transforming function differed somewhat from that of adenovirus E1A in that E7 was also able to transform established mouse cells. Examination of the amino acid sequence of HPV-16 E7 revealed striking similarities with conserved domains 1 and 2 of adenovirus E1A proteins.
临床和流行病学数据表明,人乳头瘤病毒(HPV)在某些肛门生殖器恶性肿瘤中具有病因学作用,其中HPV - 16在宫颈癌中检出频率最高(超过60%)。HPV - 16在癌症中活跃转录;最丰富的转录本定位于E6和E7早期开放阅读框。有证据表明,HPV - 16 E7开放阅读框编码的转录反式激活和细胞转化功能类似于腺病毒E1A蛋白。具体而言,HPV - 16 E7基因产物可反式激活腺病毒E2启动子,并与活化的ras癌基因协同作用,转化原代新生大鼠肾细胞。E7的转化功能与腺病毒E1A有所不同,因为E7也能够转化已建立的小鼠细胞。对HPV - 16 E7氨基酸序列的检查揭示了与腺病毒E1A蛋白保守结构域1和2的显著相似性。