Journal article
Ubiquitination Regulates the Neuroprotective Function of the Deubiquitinase Ataxin-3 in Vivo
The Journal of biological chemistry, Vol.288(48), pp.34460-34469
11/29/2013
DOI: 10.1074/jbc.M113.513903
PMCID: PMC3843061
PMID: 24106274
Abstract
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.
Background: Ubiquitination of ataxin-3 enhances its DUB activity in vitro, but it is unknown whether it controls its function in intact organisms.
Results: Ubiquitination at lysine 117 regulates the neuroprotective function of ataxin-3 in Drosophila.
Conclusion: Ataxin-3 ubiquitination is a critical regulator of its in vivo functions.
Significance: Ubiquitination may constitute a general regulatory mechanism of DUB activities in vivo.
Details
- Title: Subtitle
- Ubiquitination Regulates the Neuroprotective Function of the Deubiquitinase Ataxin-3 in Vivo
- Creators
- Wei-Ling Tsou - Wayne State UniversityAaron A. Burr - Wayne State UniversityMichelle Ouyang - Wayne State UniversityJessica R. Blount - Wayne State UniversityK.Matthew Scaglione - Medical College of WisconsinSokol V. Todi - Wayne State University
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.288(48), pp.34460-34469
- Publisher
- Elsevier Inc
- DOI
- 10.1074/jbc.M113.513903
- PMID
- 24106274
- PMCID
- PMC3843061
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Language
- English
- Date published
- 11/29/2013
- Academic Unit
- Radiology
- Record Identifier
- 9984697619602771
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