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.
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 HPV 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.
Georgopoulos
N T
NT
School of Biochemistry and Molecular Biology, University of Leeds, UK.
Proffitt
J L
JL
Blair
G E
GE
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D017500:Adenovirus E1A Proteins / Q000502:physiology; D000818:Animals; D004268:DNA-Binding Proteins; D005347:Fibroblasts; D015967:Gene Expression Regulation, Viral; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000502:physiology*; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000502:physiology*; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014158:Transcription, Genetic; D014162:Transfection; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D017500:Adenovirus E1A Proteins; D004268:DNA-Binding Proteins; C085208:E7 protein, Human papillomavirus 6b; C052633:E7 protein, Human papillomavirus type 18; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D011993:Recombinant Fusion Proteins; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse; C486172:Tap1 protein, rat; D014763:Viral Matrix Proteins; C059731:oncogene protein E7, Human papillomavirus type 16; C066076:oncogene protein E7, Human papillomavirus type 8