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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Tsou, W-L; Burr, AA; Ouyang, M; Blount, JR; Scaglione, KM; Todi, SV

Published Date

  • November 29, 2013

Published In

Volume / Issue

  • 288 / 48

Start / End Page

  • 34460 - 34469

PubMed ID

  • 24106274

Pubmed Central ID

  • PMC3843061

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

Digital Object Identifier (DOI)

  • 10.1074/jbc.M113.513903


  • eng

Conference Location

  • United States