Feedback regulation between orphan nuclear receptor TR2 and human papilloma virus type 16

The human TR2 orphan receptor (TR2), initially isolated from testis and pro state cDNA libraries, is a member of the steroid receptor superfamily. TR2 can regulate several target genes via binding to a consensus response eleme nt (AGGTCA) in direct repeat orientation (AGGTCAX((n))AGGTCA, n = 0-6). Her e show that TR2 is able to induce the expression of human papilloma virus t ype 16 (HPV-16) genes via binding to a DR4 response element in the long con trol region of HPV-16. Additionally, one of the HPV-16 gene products, the E 6 oncogene, regulates TR2 gene expression. A likely mechanism for this regu lation involves E6-mediate-degradation of the tumor suppressor p53, a prote in known to suppress TR2 expression. Together our data provide evidence for feedback regulation between TR2 and HPV-16, which represents a novel regul atory pathway involving a member of the steroid receptor superfamily and th e HPV-16 DNA tumor virus.