The E2 proteins from high- and low-risk human papillomavirus types differ in their ability to bind p53 and induce apoptotic cell death.

Joanna Louise Parish, A Kowalczyk, H-T Chen, GE Roeder, R Sessions, M Buckle, K Gaston

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

The E2 proteins from oncogenic (high-risk) human papillomaviruses (HPVs) can induce apoptotic cell death in both HPV-transformed and non-HPV-transformed cells. Here we show that the E2 proteins from HPV type 6 (HPV6) and HPV11, two nononcogenic (low-risk) HPV types, fail to induce apoptosis. Unlike the high-risk HPV16 E2 protein, these low-risk E2 proteins fail to bind p53 and fail to induce p53-dependent transcription activation. Interestingly, neither the ability of p53 to activate transcription nor the ability of p53 to bind DNA, are required for HPV16 E2-induced apoptosis in non-HPV-transformed cells. However, mutations that reduce the binding of the HPV16 E2 protein to p53 inhibit E2-induced apoptosis in non-HPV-transformed cells. In contrast, the interaction between HPV16 E2 and p53 is not required for this E2 protein to induce apoptosis in HPV-transformed cells. Thus, our data suggest that this high-risk HPV E2 protein induces apoptosis via two pathways. One pathway involves the binding of E2 to p53 and can operate in both HPV-transformed and non-HPV-transformed cells. The second pathway requires the binding of E2 to the viral genome and can only operate in HPV-transformed cells.

Original languageEnglish
Pages (from-to)4580-4590
Number of pages11
JournalJournal of Virology
Volume80
Issue number9
DOIs
Publication statusPublished - May 2006

Keywords

  • CERVICAL-CARCINOMA CELLS
  • NONONCOGENIC HUMAN-PAPILLOMAVIRUS
  • TUMOR-SUPPRESSOR PROTEIN
  • DNA-BINDING
  • ONCOGENE EXPRESSION
  • HUMAN KERATINOCYTES
  • GROWTH-INHIBITION
  • E6 ONCOPROTEIN
  • HELA-CELLS
  • HPV 16

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