Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc

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Proceedings of the National Academy of Sciences. 2013, 110(22), pp. 8888-8893. ISSN 0027-8424. eISSN 1091-6490. Available under: doi: 10.1073/pnas.1302792110
Zusammenfassung

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.

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ISO 690KÜHNLE, Simone, Benedikt MOTHES, Konstantin MATENTZOGLU, Martin SCHEFFNER, 2013. Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc. In: Proceedings of the National Academy of Sciences. 2013, 110(22), pp. 8888-8893. ISSN 0027-8424. eISSN 1091-6490. Available under: doi: 10.1073/pnas.1302792110
BibTex
@article{Kuhnle2013-05-28ubiqu-25129,
  year={2013},
  doi={10.1073/pnas.1302792110},
  title={Role of the ubiquitin ligase E6AP/UBE3A in controlling levels of the synaptic protein Arc},
  number={22},
  volume={110},
  issn={0027-8424},
  journal={Proceedings of the National Academy of Sciences},
  pages={8888--8893},
  author={Kühnle, Simone and Mothes, Benedikt and Matentzoglu, Konstantin and Scheffner, Martin}
}
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    <dcterms:abstract xml:lang="eng">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.</dcterms:abstract>
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