Transcriptional regulation of the major histocompatibility complex (MHC) class I heavy chain, TAP1 and LMP2 genes by the human papillomavirus (HPV) type 6b, 16 and 18 E7 oncoproteins
Transcriptional regulation of the major histocompatibility complex (MHC) class I heavy chain, TAP1 and LMP2 genes by the human papillomavirus (HPV) type 6b, 16 and 18 E7 oncoproteins
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DOI：
10.1038/sj.onc.1203860
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发表时间：
2000-10-05
期刊：
影响因子：
8
通讯作者：
Blair, GE
中科院分区：
文献类型：
--
作者：
Georgopoulos, NT;Proffitt, JL;Blair, GE
我们已经研究了高危型人乳头瘤病毒（HPV）16型和18型的E7蛋白和致癌腺病毒（Ad）12型E1 A蛋白共享下调抗原加工和呈递途径组分表达的能力的可能性，作为在诱导细胞转化过程中逃避免疫监视的常见策略。HPV 18 E7癌蛋白的表达，如Ad 12 E1 A，导致主要组织相容性复合体（MHC）I类重链启动子的抑制，以及调节编码与抗原加工亚基1（TAP 1）和蛋白酶体亚基低分子量蛋白2（LMP 2）相关的转运蛋白的基因表达的双向启动子的抑制，HPV 16 E7也引起I类重链启动子活性的降低，然而它对双向启动子的活性没有任何显著影响。有趣的是，低风险I-IPV 6 b E7蛋白的表达导致MHC I类重链启动子活性的增加，同时抑制TAP 1/LMP 2启动子。I类途径的干扰也可以解释低风险HPV诱导良性病变的能力。
We have examined the possibility that the E7 proteins of the high-risk human papillomavirus (HPV) type 16 and 18 and the oncogenic adenovirus (Ad) type 12 E1A protein share the ability to down-regulate the expression of components of the antigen processing and presentation pathway, as a common strategy in the evasion of immune surveillance during the induction of cell transformation. Expression of the HPV 18 E7 oncoprotein, like Ad 12 E1A, resulted in repression of the major histocompatibility complex (MHC) class I heavy chain promoter, as well as repression of a bidirectional promoter that regulates expression of the genes encoding the transporter associated with antigen processing subunit 1 (TAP1) and a proteasome subunit, low molecular weight protein 2 (LMP2), HPV 16 E7 also caused a reduction in class I heavy chain promoter activity, however it did not have any significant effect on the activity of the bidirectional promoter. Interestingly, expression of the low-risk I-IPV 6b E7 protein resulted in an increase in MHC class I heavy chain promoter activity, while repressing the TAP1/LMP2 promoter, Interference with the class I pathway could also explain the ability of low-risk HPVs in inducing benign lesions.