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Expression of the HPV E7 oncoprotein mimics but does not evoke a p53-dependent cellular DNA damage response pathway

D L Jones1, D A Thompson, E Suh-Bürgmann

  • 1Harvard Center for Cancer Biology, Massachusetts General Hospital, Boston, Massachusetts, 02115, USA.

Virology
|June 15, 1999
PubMed

Insights

Human papillomavirus E7 oncoprotein impacts cell cycle regulators. E7 destabilizes retinoblastoma protein (pRB) and increases p21(cip1) levels, independent of p53 activity, revealing distinct pathways from DNA damage responses.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Virology

Background:

  • Human papillomavirus (HPV) oncoproteins, particularly E7, are implicated in cellular dysregulation.
  • The retinoblastoma protein (pRB) and p53 tumor suppressors, along with p21(cip1), are critical cell cycle regulators.
  • Alterations in pRB, p53, and p21(cip1) levels are observed in both HPV infection and DNA damage responses.

Purpose of the Study:

  • To investigate whether HPV E7 oncoprotein expression triggers the p53-dependent DNA damage signaling pathway.
  • To elucidate the mechanisms underlying E7-mediated changes in pRB, p53, and p21(cip1) protein levels.

Main Methods:

  • Expression of HPV E7 oncoprotein in pre-immortal human fibroblasts.
  • Analysis of protein abundances for pRB, p53, and p21(cip1).
  • Assessment of p53 dependency and apoptosis induction in relation to E7 effects.

Main Results:

  • E7 expression destabilizes pRB independently of p53 activity and apoptosis.
  • E7-induced increases in p21(cip1) levels are largely p53-independent, involving protein stabilization.
  • DNA damage-induced decreases in pRB involve transcriptional downregulation of RB gene expression, contrasting with E7 effects.

Conclusions:

  • HPV E7 oncoprotein utilizes distinct mechanisms to alter cell cycle regulators compared to DNA damage pathways.
  • E7-mediated pRB destabilization and p21(cip1) stabilization are largely independent of p53.
  • Understanding these divergent pathways is crucial for comprehending HPV-driven oncogenesis.

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