The role of the E6-p53 interaction in the molecular pathogenesis of HPV.
Human papillomaviruses (HPVs) are associated with a number of clinical conditions, of which the most serious is cervical carcinoma. The E6 protein of the oncogenic, mucosal-specific HPV types has been shown to complex with p53 and, as a result, target it for rapid proteasome-mediated degradation. As a consequence, p53's growth-arrest and apoptosis-inducing activities are abrogated. Since p53 is frequently wild type in cervical cancers, unlike other cancers in which it is often mutated, the notion has arisen that E6's activity with respect to p53 is equivalent to an inactivating mutation of p53. In addition, several studies have shown that the pathways both upstream and downstream of p53 are intact in cervical cancers; this suggests the potential importance of the E6 - p53 interaction for therapeutic intervention. However, like all viral oncoproteins, E6 is a multifunctional protein and a plethora of other cellular targets has been identified. Indeed, E6's interactions with some of these additional targets appear to be equally important in the pathogenesis of HPV, and may also represent valid targets for therapeutic intervention.
Thomas
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International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
Pim
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Banks
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D017398:Alternative Splicing; D000818:Animals; D002453:Cell Cycle; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D027383:Papillomaviridae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D011110:Polymorphism, Genetic / Q000235:genetics; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy / Q000821:virology; D014779:Virus Replication / Q000235:genetics
C118860:E6 protein, Human papillomavirus type 6; D009856:Oncogene Proteins, Viral; D016159:Tumor Suppressor Protein p53