title: Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc.
abstract: Inactivation of the ubiquitin ligase E6 associated protein (E6AP) encoded by the UBE3A gene has been associated with development of the Angelman syndrome. Recently, it was reported that in mice, loss of E6AP expression results in increased levels of the synaptic protein Arc and a concomitant impaired synaptic function, providing an explanation for some phenotypic features of Angelman syndrome patients. Accordingly, E6AP has been shown to negatively regulate activity-regulated cytoskeleton-associated protein (Arc) and it has been suggested that E6AP targets Arc for ubiquitination and degradation. In our study, we provide evidence that Arc is not a direct substrate for E6AP and binds only weakly to E6AP, if at all. Furthermore, we show that down-regulation of E6AP expression stimulates estradiol-induced transcription of the Arc gene. Thus, we propose that Arc protein levels are controlled by E6AP at the transcriptional rather than at the posttranslational level.
authors.affiliation: Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
authors.forename: Simone
authors.initials: S
authors.lastname: Kühnle
authors.forename: Benedikt
authors.initials: B
authors.lastname: Mothes
authors.forename: Konstantin
authors.initials: K
authors.lastname: Matentzoglu
authors.forename: Martin
authors.initials: M
authors.lastname: Scheffner
mesh_terms: D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D004926:Escherichia coli; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D008156:Luciferases; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D013569:Synapses / Q000378:metabolism*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: D003598:Cytoskeletal Proteins; D017931:DNA Primers; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein; D004958:Estradiol; D008156:Luciferases; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases