The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway

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2012
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Bett, John S.
Kanuga, Naheed
Richet, Emma
Cheetham, Michael E.
van der Spuy, Jacqueline
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PLoS ONE. 2012, 7(2), e30866. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0030866
Zusammenfassung

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.

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570 Biowissenschaften, Biologie
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ISO 690BETT, John S., Naheed KANUGA, Emma RICHET, Gunter SCHMIDTKE, Marcus GRÖTTRUP, Michael E. CHEETHAM, Jacqueline VAN DER SPUY, 2012. The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway. In: PLoS ONE. 2012, 7(2), e30866. eISSN 1932-6203. Available under: doi: 10.1371/journal.pone.0030866
BibTex
@article{Bett2012inher-22007,
  year={2012},
  doi={10.1371/journal.pone.0030866},
  title={The inherited blindness protein AIPL1 regulates the ubiquitin-like FAT10 pathway},
  number={2},
  volume={7},
  journal={PLoS ONE},
  author={Bett, John S. and Kanuga, Naheed and Richet, Emma and Schmidtke, Gunter and Gröttrup, Marcus and Cheetham, Michael E. and van der Spuy, Jacqueline},
  note={Article Number: e30866}
}
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