NF-κB signalling is attenuated by the E7 protein from cutaneous human papillomaviruses

Luise M Byg1, Jessica Vidlund, Natasa Vasiljevic

  • 1The DNA Tumour Virus Group, Department of Cellular and Molecular Medicine, University of Copenhagen, Denmark.

Virus Research
|July 11, 2012
PubMed

Insights

Cutaneous human papillomaviruses (HPVs) E7 proteins inhibit the NF-κB pathway, similar to high-risk Alpha-HPV types. This suggests a role for Beta- and Gamma-HPV E7 in non-melanoma skin cancer development.

Area of Science:

  • Oncology
  • Virology
  • Molecular Biology

Background:

  • High-risk Alpha-papillomaviruses (HPVs) cause cervical cancer and their E7 proteins modulate the NF-κB pathway.
  • Cutaneous Beta-papillomaviruses are linked to non-melanoma skin cancer, but their effect on the NF-κB pathway is unknown.

Purpose of the Study:

  • To investigate whether E7 proteins from cutaneous Beta- and Gamma-papillomaviruses can modulate the NF-κB pathway.
  • To determine if these E7 proteins interact with IKKα and IKKβ.

Main Methods:

  • E7 proteins from seven cutaneous HPV types (Beta genus: HPV-20, -37, -38, -92, -93, -96; Gamma genus: HPV-4) were expressed in U2OS cells.
  • NF-κB pathway activity was assessed.
  • Interactions with IKKα and IKKβ were examined.

Main Results:

  • E7 proteins from all tested cutaneous HPV types inhibited NF-κB activity.
  • Cutaneous HPV E7 proteins interacted with IKKα but not IKKβ.
  • This inhibitory effect mirrors that of high-risk Alpha-HPV16 E7.

Conclusions:

  • E7 proteins from Beta- and Gamma-papillomaviruses can inhibit the NF-κB pathway.
  • This inhibition, mediated by IKKα interaction, may contribute to the pathogenesis of non-melanoma skin cancers.

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