Repression of MHC class I transcription by HPV16E7 through interaction with a putative RXRbeta motif and NF-kappaB cytoplasmic sequestration.
Down-regulation of transcription of the MHC class I genes in HPV16 tumorigenic cells is partly due to HPV16E7 associated with the MHC class I promoter and repressed chromatin activation. In this study, we further demonstrated that HPV16E7 is physically associated with a putative RXRbeta binding motif (GGTCA) of the proximal promoter of the MHC class I genes by using reporter transcriptional assays and chromatin immunoprecipitation assays. Our data also provide evidence that HPV16E7 inhibits TNF-alpha-induced up-regulation of MHC class I transcription by impaired nuclear translocation of NF-kappaB. More importantly, CaSki tumor cells treated with TSA and transfected with the constitutively active mutant form of IKK-alpha (which can activate NF-kappaB directly) showed a maximal level of up-regulation of MHC-I expression. Taken together, our results suggest that HPV16E7 may employ two independent mechanisms to ensure that either the constitutive or inducible transcription of MHC class I genes is down-regulated.
Li
Hui
H
Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, PR China.
Zhan
Tailan
T
Li
Chang
C
Liu
Mugen
M
Wang
Qing K
QK
D020816:Amino Acid Motifs; D045744:Cell Line, Tumor; D002472:Cell Transformation, Viral / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I; D015789:HLA-A2 Antigen / Q000235:genetics; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D050725:Papillomavirus E7 Proteins; D011401:Promoter Regions, Genetic; D049230:Retinoid X Receptor beta / Q000378:metabolism*; D014158:Transcription, Genetic; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology
D015789:HLA-A2 Antigen; D016328:NF-kappa B; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D049230:Retinoid X Receptor beta; C059731:oncogene protein E7, Human papillomavirus type 16; D006655:Histone Deacetylases