Identification and characterization of target proteins of the ubiquitin-protein ligase E6-AP (Identifizierung von Zielproteinen der putativen Ubiquitin-Proteinligase E6-AP)

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The recognition of substrate proteins by the ubiquitin-conjugation system is a specific and, at least in some instances, regulated event. It is widely assumed that ubiquitin-conjugating enzymes and, in particular, ubiquitin-protein ligases play a major role in mediating substrate recognition. Over the past few years, several proteins or protein families with ubiquitinprotein ligase activity have been identified including the SCF family and the hect domain family. Members of the hect domain family are found in all eukaryotic organisms so far examined and the human genome encodes at least 20 different hect domain proteins. However, the physiologic function and the substrates of most hect domain proteins are unknown at present. The principal aim of this proposal is the identification and characterization of target proteins of two human hect domain proteins, E6-AP and hsORFK/HectH3. Interestingly, loss of function of the E6-AP gene results in a neurodegenerative disorder, the Angelman Syndrome. Thus, these studies should contribute to the elucidation of the physiologic role of these proteins in general and of the role of disregulated protein degradation in the development of the Angelman Syndrome in particular.