STRUCTURAL FEATURES OF PAPILLOMAVIRUS E6 ONCOPROTEINS

乳头瘤病毒是全世界妇女中最常见的致命癌症--宫颈癌的病原体。因此，它们的癌蛋白转化细胞的机制具有生物学意义和医学意义。肿瘤相关乳头状瘤病毒的一个重要功能是靶向降解P53抑癌基因，这是通过E6癌蛋白与细胞泛素连接酶E6AP的结合而介导的。在这个提案中，我们将确定16E6、E6AP和P53的结构特征，这些结构特征决定了这些蛋白质中的每一个形成复合体的能力。然后，我们将利用本研究中获得的突变体来确定与E6相互作用的细胞蛋白的生物学相关性，并阐明P53肿瘤抑制因子降解所需的分子特征。

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.