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

L L Collins1, D L Lin, X M Mu

  • 1George Whipple Laboratory for Cancer Research, Department of Pathology, University of Rochester Medical Center, Rochester, New York 14642, USA.

The Journal of Biological Chemistry
|May 19, 2001
PubMed

Insights

The human TR2 orphan receptor (TR2) regulates human papillomavirus type 16 (HPV-16) genes. HPV-16 E6 oncogene affects TR2 expression, revealing a novel feedback loop between the steroid receptor superfamily and HPV-16.

Area of Science:

  • Molecular Biology
  • Virology
  • Endocrinology

Background:

  • The human TR2 orphan receptor (TR2) is a member of the steroid receptor superfamily, known to regulate gene expression through DNA binding.
  • TR2 binds to specific response elements in a direct repeat orientation to control target genes.

Purpose of the Study:

  • To investigate the interaction between the human TR2 orphan receptor and human papillomavirus type 16 (HPV-16).
  • To elucidate the regulatory mechanisms governing the expression of TR2 and HPV-16 genes.

Main Methods:

  • Analysis of TR2 binding to response elements in the HPV-16 genome.
  • Investigation of HPV-16 E6 oncogene's effect on TR2 gene expression.
  • Assessment of the role of p53 in the E6-mediated regulation of TR2.

Main Results:

  • TR2 induces the expression of HPV-16 genes by binding to a DR4 response element in the HPV-16 long control region.
  • The HPV-16 E6 oncogene regulates TR2 gene expression.
  • E6-mediated degradation of tumor suppressor p53 likely contributes to TR2 expression regulation.

Conclusions:

  • A novel feedback regulatory pathway exists between TR2 and HPV-16.
  • This pathway involves a steroid receptor superfamily member and the HPV-16 DNA tumor virus.
  • The findings shed light on the complex interplay between viral oncogenes and host nuclear receptors.

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