A comparative analysis of the interactions of the E6 proteins from cutaneous and genital papillomaviruses with p53 and E6AP in correlation to their transforming potential

Virology
M ElbelT Iftner

Abstract

Common necessity for all papillomaviruses is to induce DNA synthesis in quiescent cells. This is commonly achieved by the E7 gene product, which interferes with the function of members of the retinoblastoma family controlling transition from the G1-phase to the S-phase of the cell cycle. Uncontrolled entry into S-phase activates, however, negative growth control signals which have to be bypassed to achieve production of progeny viruses. In addition to inherent activities of the E7 protein, high risk genital types encode an E6 protein that overcomes p53-mediated G1-arrest and apoptosis in concert with the cellular factor E6AP by targeting p53 for the enhanced ubiquitin-dependent degradation. The key question, which of these functions of genital E6 and E7 proteins is responsible for the carcinogenic phenotype, is still not completely answered. In contrast to high risk genital types no immortalizing or transforming activities have been found for the E7 proteins of the high risk cutaneous HPV8 and 47. On the other hand the ability of the E6 protein to transform established rodent fibroblasts seems to be a property shared by high risk genital and cutaneous types. To examine the existence of a common E6-mediated transforming pathway ...Continue Reading

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