Feedback regulation between orphan nuclear receptor TR2 and human papilloma virus type 16.
The human TR2 orphan receptor (TR2), initially isolated from testis and prostate cDNA libraries, is a member of the steroid receptor superfamily. TR2 can regulate several target genes via binding to a consensus response element (AGGTCA) in direct repeat orientation (AGGTCAX((n))AGGTCA, n = 0-6). Here we show that TR2 is able to induce the expression of human papilloma virus type 16 (HPV-16) genes via binding to a DR4 response element in the long control region of HPV-16. Additionally, one of the HPV-16 gene products, the E6 oncogene, regulates TR2 gene expression. A likely mechanism for this regulation involves E6-mediated degradation of the tumor suppressor p53, a protein known to suppress TR2 expression. Together our data provide evidence for feedback regulation between TR2 and HPV-16, which represents a novel regulatory pathway involving a member of the steroid receptor superfamily and the HPV-16 DNA tumor virus.
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George Whipple Laboratory for Cancer Research, Department of Pathology, University of Rochester Medical Center, Rochester, New York 14642, USA.
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Chang
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D000818:Animals; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004742:Enhancer Elements, Genetic; D005246:Feedback; D006801:Humans; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D027383:Papillomaviridae / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D013937:Thymidine Kinase / Q000235:genetics
C539822:NR2C1 protein, human; D057107:Nuclear Receptor Subfamily 2, Group C, Member 1; D011988:Receptors, Thyroid Hormone; D013937:Thymidine Kinase