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Published on: March 8, 2012
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.
Abstract:
The high-risk Alpha-types of human papillomavirus (HPV) are the causative agent of cervical cancer, which is the second major cause of death among women worldwide. Recent investigations have shown that E7 from the Alpha-papillomavirus HPV-16 interacts with IKKα and IKKβ of the IKK complex in the NF-κB pathway leading to an attenuation of the activity. There is a possible link between development of non-melanoma skin cancer and cutaneous Beta-papillomavirus but if these HPV types attenuate the NF-κB pathway is unclear. Seven different E7 proteins, representing four out of the five different species of the Beta genus (HPV-20, -37, -38, -92, -93 and -96) and one from the Gamma genus (HPV-4) were investigated for potential modulation of the NF-κB pathway in U2OS cells. Our results demonstrate that E7 from all the cutaneous HPV types were capable of inhibiting the NF-κB activity as well as E7 from HPV-16. In addition, E7 proteins from the cutaneous HPV types demonstrated interaction with IKKα but not with IKKβ. The deregulation of the NF-κB pathway by cutaneous HPVs might contribute to the pathogenesis of non-melanoma skin cancers and its precursors.
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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