Molecular mechanisms underlying human papillomavirus E6 and E7 oncoprotein-induced cell transformation

Mutat Res Rev Mutat Res. 2017 Apr-Jun:772:23-35. doi: 10.1016/j.mrrev.2016.08.001. Epub 2016 Aug 5.

Abstract

Human papillomaviruses (HPVs) are the causative agents of 5% of all human cancers, with cervical cancer being the most important. Two viral oncoproteins, E6 and E7, are essential for the development and maintenance of malignancy. Both proteins function by targeting critical pathways that are essential for maintaining cellular homeostasis. As a consequence of these activities, this produces an environment that is favourable for the normal viral life cycle, but when perturbed, can result in the initiation of changes to the host cell, which ultimately results in the development of a malignancy. In this review we discuss the role of these different functions of the viral oncoproteins during the viral life cycle and carcinogenesis, with an emphasis on how induction of DNA damage by the viral oncoproteins, in conjunction with the stem like nature of the target cells, can ultimately result in the development of cancer.

Keywords: Cervical Cancer; Cervical Cancer Stem Cells; HPV; HPV E6; HPV E7.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis
  • Cell Transformation, Neoplastic / genetics*
  • DNA Damage
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Epigenesis, Genetic
  • Humans
  • Neoplasms / pathology
  • Neoplasms / virology
  • Neoplastic Stem Cells / virology
  • Oncogene Proteins, Viral / genetics
  • Oncogene Proteins, Viral / metabolism*
  • Papillomaviridae / genetics*
  • Papillomavirus E7 Proteins / genetics
  • Papillomavirus E7 Proteins / metabolism*
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / virology
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*

Substances

  • DNA-Binding Proteins
  • E6 protein, Human papillomavirus type 16
  • E6 protein, Human papillomavirus type 18
  • Oncogene Proteins, Viral
  • Papillomavirus E7 Proteins
  • Repressor Proteins