engleski

Oncogenic Potential of Naturally Occurring HPV- 16 E6 Variants

To date, approximately 200 different human papillomavirus types were shown to infect human epithelial cells. Fifteen of these have been classified as oncogenic or high-risk HPV types because of their etiological role in the development of cervical cancer, anogenital cancers, and some head-and-neck carcinomas. HPV-16 type was classified as the most prevalent viral type in causing cancer. The virus encodes two major oncoproteins, E6 and E7, which in cooperation are responsible for malignant progression. By forming interactions with many substrates E6 regulates various cellular pathways and contributes towards later stages of HPV-dependent tumorigenicity. The main oncogenic activity of high-risk E6 is ability to interact with the tumor suppressor p53 and induce its proteasome-mediated degradation. Along with p53 targeting E6 contributes to malignant progression via other important functions. Some of these include targeting of pro-apoptotic factors BAX and BAK, and PDZ-domain containing proteins. Interestingly, there are many HPV-16 E6 intra- type genetic variants identified and a number of them were reported be more frequently associated with HPV-mediated cancers, implying there are some likely very important differences in the oncogenic potentials of E6 variants to drive malignant progression. This is likely to be due to the differences in abilities of these variants to interact with their substrates and manipulate various cellular pathways. In this study, we performed a functional analysis of three naturally occurring HPV-16 E6 variants with different levels of prevalence in cervical cancers. The E6 variants were evaluated for their biochemical activities in various in vitro assays, in which we investigated how the amino acid changes in these variants might reflect upon their capacities to interact and regulate protein expression of some of the known E6 targets.

Human papillomavirus ; E6 oncoprotein ; E6 variants ; cancer ; transformation

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