HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs

Michelle S. Longworth, Regina Wilson, Laimonis A. Laimins*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

The E7 proteins of human papillomaviruses (HPVs) contribute to oncogenesis by associating with Rb family members as well class I histone deacetylases (HDACs). The binding of HDACs is also important for the maintenance of viral episomes during the differentiation-dependent productive life cycle. The effects of E7 and other viral proteins on E2F family members were examined in differentiating keratinocytes. E7 was found to specifically activate E2F2 transcription in suprabasal keratinocytes through its ability to bind HDACs. Chromatin immunoprecipitation assays demonstrated that, in differentiating cells, E7 acts to inhibit HDAC binding to the E2F2 promoter resulting in activation of expression. Reduction of E2F2 levels through the use of siRNA confirmed that E2F2 expression facilitated HPV replication but its loss did not affect cell proliferation. Our study demonstrates a mechanism by which binding of HDACs to E7 directly modulates viral replication and identifies E2F2 as a possible target for antiviral therapies.

Original languageEnglish (US)
Pages (from-to)1821-1830
Number of pages10
JournalEMBO Journal
Volume24
Issue number10
DOIs
StatePublished - May 18 2005

Keywords

  • E2F2
  • E7
  • Histone deacetylase
  • Human papillomavirus

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'HPV31 E7 facilitates replication by activating E2F2 transcription through its interaction with HDACs'. Together they form a unique fingerprint.

Cite this