STRUCTURAL FEATURES OF PAPILLOMAVIRUS E6 ONCOPROTEINS

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Papillomaviruses are causative agents in the most prevalent lethal cancer in women world-wide: cervical cancer. As such, the mechanisms by which their oncoproteins transform cells is biologically interesting and medically significant. One important function of the cancer associated papillomaviruses is the targeted degradation of the p53 tumor suppressor, which is mediated by the association of the E6 oncoprotein with the cellular ubiquitin ligase E6AP. In this proposal we will determine the structural features of 16E6, E6AP, and p53 that determine the capacity of each of these proteins to form a complex. We will then utilize the mutants derived in this study to determine the biological relevance of cellular proteins that interact with E6, and elucidate the molecular features required for the degradation of the p53 tumor suppressor.