Ubiquitination regulates the neuroprotective function of the deubiquitinase ataxin-3 in vivo. J Biol Chem 2013 Nov 29;288(48):34460-9
Date
10/10/2013Pubmed ID
24106274Pubmed Central ID
PMC3843061DOI
10.1074/jbc.M113.513903Abstract
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.
Author List
Tsou WL, Burr AA, Ouyang M, Blount JR, Scaglione KM, Todi SVMESH terms used to index this publication - Major topics in bold
AnimalsAtaxin-3
Drosophila Proteins
Drosophila melanogaster
Gene Expression Regulation, Developmental
Lysine
Mice
Mice, Knockout
Mutation
Nerve Tissue Proteins
Nuclear Proteins
Pigmentation
Proteolysis
Repressor Proteins
Retina
Ubiquitin
Ubiquitin-Protein Ligases
Ubiquitin-Specific Proteases
Ubiquitination
