Bett, JS;
Kanuga, N;
Richet, E;
Schmidtke, G;
Groettrup, M;
Cheetham, ME;
van der Spuy, J;
(2012)
The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway.
PLoS One
, 7
(2)
, Article e30866. 10.1371/journal.pone.0030866.
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Abstract
Mutations in AIPL1 cause the inherited blindness Leber congenital amaurosis (LCA). AIPL1 has previously been shown to interact with NUB1, which facilitates the proteasomal degradation of proteins modified with the ubiquitin-like protein FAT10. Here we report that AIPL1 binds non-covalently to free FAT10 and FAT10ylated proteins and can form a ternary complex with FAT10 and NUB1. In addition, AIPL1 antagonised the NUB1-mediated degradation of the model FAT10 conjugate, FAT10-DHFR, and pathogenic mutations of AIPL1 were defective in inhibiting this degradation. While all AIPL1 mutants tested still bound FAT10-DHFR, there was a close correlation between the ability of the mutants to interact with NUB1 and their ability to prevent NUB1-mediated degradation. Interestingly, AIPL1 also co-immunoprecipitated the E1 activating enzyme for FAT10, UBA6, suggesting AIPL1 may have a role in directly regulating the FAT10 conjugation machinery. These studies are the first to implicate FAT10 in retinal cell biology and LCA pathogenesis, and reveal a new role of AIPL1 in regulating the FAT10 pathway.
| Type: | Article |
|---|---|
| Title: | The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0030866 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0030866 |
| Language: | English |
| Additional information: | © 2012 Bett et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC3274541 This work was supported by grants from the Wellcome Trust (GR077929MA) and the German Research Foundation (DFG) (GR1517/2-3 and GR1517/3-1). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | Carrier Proteins, Cell Line, Tumor, Eye Proteins, Humans, Leber Congenital Amaurosis, Mutation, Retina, Transcription Factors, Ubiquitins |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1340729 |
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