HPV E6

HPVs have circular, double-stranded DNA genomes that are approximately 8 kb in size and encode eight genes, of which E6 and E7 have transforming properties. These proteins have pleiotropic functions, such as transmembrane signaling, regulation of the cell cycle, transformation of established cell lines, immortalization of primary cell line and regulation of chromosomal stability. The viral E6 and E7 oncoproteins are necessary for malignant conversion. The E6 protein consists of 158 amino acid residues and contains two zinc-finger binding motifs. The E6 protein is thought to promote cell proliferation by stimulating degradation of the tumor suppressor p53 protein via the formation of a trimeric complex comprising E6, p53 and the cellular ubiquitination enzyme E6-AP. E6-stimulated degradation interferes with such biological functions of p53; thus perturbing the control of cell cycle progression, leading finally to increased tumor cell growth. Although it is commonly accepted that the ability of high-risk type HPV E6 to target p53 for degradation contributes to virus-induced cellular transformation, it is also clear that the E6 protein has oncogenic activities that are independent of p53.