Caister Academic Press

Molecular Mechanisms of E6 and E7 Oncoproteins From Human Papillomaviruses in Cellular Transformation

Massimo Tommasino
from: DNA Tumour Viruses: Virology, Pathogenesis and Vaccines (Edited by: Sally Roberts). Caister Academic Press, U.K. (2018) Pages: 59-78.

Abstract

The small double-stranded DNA human papillomaviruses (HPVs) form a family of approximately 200 viruses. They can infect the epithelia of the genital and upper respiratory tracts and the skin and are classified into several genera based on their DNA sequence. A small number belonging to genus alpha, referred to as mucosal high-risk (HR) HPV types, are clearly associated with human carcinogenesis. In particular, HR HPV16 and HPV18 are the most carcinogenic types, responsible for a large proportion of HPV-positive anogenital cancers. A vast number of studies have demonstrated that the products of two early genes, E6 and E7, play a key role in cellular transformation and cancer development. Both oncoproteins are very small molecules and do not have any enzymatic activities, but exert their biological properties by interacting with a large number of cellular proteins. These interactions result in modification of the activities of the cellular proteins, which, in some cases, are targeted to degradation via the proteasome pathway. The most studied examples are the ability of HR HPV E6 and E7 to induce degradation of p53 and pRb, respectively. Inactivation of these key tumour suppressors strongly alters cellular gene expression, leading to chromosomal instability and cellular transformation.

Despite the great knowledge of the biology of mucosal HR HPV types, additional research is needed to characterize the biology of the majority of HPV types that have been poorly investigated so far, with a final aim of evaluating their potential roles in other human diseases read more ...

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