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Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo.

Publication ,  Journal Article
Tsou, W-L; Burr, AA; Ouyang, M; Blount, JR; Scaglione, KM; Todi, SV
Published in: J Biol Chem
November 29, 2013

Deubiquitinases (DUBs) are proteases that regulate various cellular processes by controlling protein ubiquitination. Cell-based studies indicate that the regulation of the activity of DUBs is important for homeostasis and is achieved by multiple mechanisms, including through their own ubiquitination. However, the physiological significance of the ubiquitination of DUBs to their functions in vivo is unclear. Here, we report that ubiquitination of the DUB ataxin-3 at lysine residue 117, which markedly enhances its protease activity in vitro, is critical for its ability to suppress toxic protein-dependent degeneration in Drosophila melanogaster. Compared with ataxin-3 with only Lys-117 present, ataxin-3 that does not become ubiquitinated performs significantly less efficiently in suppressing or delaying the onset of toxic protein-dependent degeneration in flies. According to further studies, the C terminus of Hsc70-interacting protein (CHIP), an E3 ubiquitin ligase that ubiquitinates ataxin-3 in vitro, is dispensable for its ubiquitination in vivo and is not required for the neuroprotective function of this DUB in Drosophila. Our work also suggests that ataxin-3 suppresses degeneration by regulating toxic protein aggregation rather than stability.

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Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

November 29, 2013

Volume

288

Issue

48

Start / End Page

34460 / 34469

Location

United States

Related Subject Headings

  • Ubiquitination
  • Ubiquitin-Specific Proteases
  • Ubiquitin-Protein Ligases
  • Ubiquitin
  • Retina
  • Repressor Proteins
  • Proteolysis
  • Pigmentation
  • Nuclear Proteins
  • Nerve Tissue Proteins
 

Citation

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Tsou, W.-L., Burr, A. A., Ouyang, M., Blount, J. R., Scaglione, K. M., & Todi, S. V. (2013). Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo. J Biol Chem, 288(48), 34460–34469. https://doi.org/10.1074/jbc.M113.513903
Tsou, Wei-Ling, Aaron A. Burr, Michelle Ouyang, Jessica R. Blount, K Matthew Scaglione, and Sokol V. Todi. “Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo.J Biol Chem 288, no. 48 (November 29, 2013): 34460–69. https://doi.org/10.1074/jbc.M113.513903.
Tsou W-L, Burr AA, Ouyang M, Blount JR, Scaglione KM, Todi SV. Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo. J Biol Chem. 2013 Nov 29;288(48):34460–9.
Tsou, Wei-Ling, et al. “Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo.J Biol Chem, vol. 288, no. 48, Nov. 2013, pp. 34460–69. Pubmed, doi:10.1074/jbc.M113.513903.
Tsou W-L, Burr AA, Ouyang M, Blount JR, Scaglione KM, Todi SV. Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo. J Biol Chem. 2013 Nov 29;288(48):34460–34469.

Published In

J Biol Chem

DOI

EISSN

1083-351X

Publication Date

November 29, 2013

Volume

288

Issue

48

Start / End Page

34460 / 34469

Location

United States

Related Subject Headings

  • Ubiquitination
  • Ubiquitin-Specific Proteases
  • Ubiquitin-Protein Ligases
  • Ubiquitin
  • Retina
  • Repressor Proteins
  • Proteolysis
  • Pigmentation
  • Nuclear Proteins
  • Nerve Tissue Proteins