title: Ubiquitin ligase E6-AP and its role in human disease.
abstract: The ubiquitin ligase E6-AP (E6-associated protein) represents a prime example for the notion that deregulated modification of proteins with ubiquitin contributes to the development of human disease: loss of E6-AP function by mutation is responsible for the development of AS (Angelman syndrome), a neurological disorder, and unscheduled activation of E6-AP by complex formation with the E6 oncoprotein of HPVs (human papillomaviruses) contributes to cervical carcinogenesis. However, while there is a considerable amount of data concerning the oncogenic properties of the E6-E6-AP complex, only little is known about the function(s) of E6-AP in neurons. This is mainly due to the fact that although some E6-AP substrates have been identified, it is at present unclear whether deregulated modification/degradation of these proteins is involved in the pathogenesis of AS. Similarly, the cellular pathways involving E6-AP remain enigmatic. To obtain insights into the physiological functions of E6-AP, we are currently employing several strategies, including quantitative affinity proteomics and RNA interference approaches. The results obtained will eventually allow the introduction of E6-AP into functional protein networks and so reveal potential targets for molecular approaches in the treatment of E6-AP-associated diseases.
authors.affiliation: Laboratory of Cellular Biochemistry, Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Matentzoglu
authors.forename: Martin
authors.initials: M
authors.lastname: Scheffner
mesh_terms: D017204:Angelman Syndrome / Q000201:enzymology / Q000235:genetics; D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009856:Oncogene Proteins, Viral / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; C052603:E6 protein, Human papillomavirus type 18; D009856:Oncogene Proteins, Viral; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases