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BioMed Research International
Volume 2018, Article ID 3180413, 14 pages
Review Article

Neuronal Proteomic Analysis of the Ubiquitinated Substrates of the Disease-Linked E3 Ligases Parkin and Ube3a

1Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV-EHU), 48940 Leioa, Spain
2Department of Biochemistry and Molecular Biology, University of the Basque Country (UPV-EHU), 01006 Vitoria-Gasteiz, Spain
3Ikerbasque, Basque Foundation for Science, Bilbao, Spain

Correspondence should be addressed to Ugo Mayor; sue.uhe@royam.ogu

Received 23 November 2017; Accepted 15 January 2018; Published 6 March 2018

Academic Editor: Louise Cheng

Copyright © 2018 Aitor Martinez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Both Parkin and UBE3A are E3 ubiquitin ligases whose mutations result in severe brain dysfunction. Several of their substrates have been identified using cell culture models in combination with proteasome inhibitors, but not in more physiological settings. We recently developed the strategy to isolate ubiquitinated proteins in flies and have now identified by mass spectrometry analysis the neuronal proteins differentially ubiquitinated by those ligases. This is an example of how flies can be used to provide biological material in order to reveal steady state substrates of disease causing genes. Collectively our results provide new leads to the possible physiological functions of the activity of those two disease causing E3 ligases. Particularly, in the case of Parkin the novelty of our data originates from the experimental setup, which is not overtly biased by acute mitochondrial depolarisation. In the case of UBE3A, it is the first time that a nonbiased screen for its neuronal substrates has been reported.