Regulation of nuclear receptor activities by two human papillomavirus type 18 oncoproteins, E6 and E7.
The human papillomavirus (HPV) E6 and E7 oncoproteins are two major proteins that remain expressing in HPV-associated human cancers. The high-risk HPVs synthesize E6 and E7 oncoproteins to alter the function of cellular regulatory proteins, such as p53 and retinoblastoma gene product, respectively. In this study, we demonstrated that HPV-18 E6 and E7 proteins were able to directly interact with some nuclear receptors (NRs), such as thyroid receptor, androgen receptor, and estrogen receptor (ER), whether or not appropriate hormones were present. The functional roles of these two oncoproteins in NRs depended on the cell type (including ligand), promoter context, and NR type. These two oncoproteins regulated ER functions through ER's AF-1, AF-2, or both. Hence, our results provide new insights into the mechanisms controlling the proliferation and immortalization of HPV infected cells by these two oncoproteins mediating through their regulatory functions in NR systems.
Wang
Wei-Ming
WM
Department of Dermatology, Tri-Service General Hospital, Taipei 114, Taiwan, ROC.
Chung
Min-Huey
MH
Huang
Shih-Ming
SM
D002460:Cell Line; D004268:DNA-Binding Proteins; D016158:Genes, p53; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D051958:Nuclear Receptor Coactivator 2; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation
D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; C052633:E7 protein, Human papillomavirus type 18; D008024:Ligands; D051958:Nuclear Receptor Coactivator 2; D009856:Oncogene Proteins, Viral; D011944:Receptors, Androgen; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D011994:Recombinant Proteins; D014157:Transcription Factors