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Citation
Tsou, W.L., Ouyang, M., Hosking, R.R., Sutton, J.R., Blount, J.R., Burr, A.A., Todi, S.V. (2015). The deubiquitinase ataxin-3 requires Rad23 and DnaJ-1 for its neuroprotective role in Drosophila melanogaster.  Neurobiol. Disease 82(): 12--21.
FlyBase ID
FBrf0230072
Publication Type
Research paper
Abstract

Ataxin-3 is a deubiquitinase and polyglutamine (polyQ) disease protein with a protective role in Drosophila melanogaster models of neurodegeneration. In the fruit fly, wild-type ataxin-3 suppresses toxicity from several polyQ disease proteins, including a pathogenic version of itself that causes spinocerebellar ataxia type 3 and pathogenic huntingtin, which causes Huntington's disease. The molecular partners of ataxin-3 in this protective function are unclear. Here, we report that ataxin-3 requires its direct interaction with the ubiquitin-binding and proteasome-associated protein, Rad23 (known as hHR23A/B in mammals) in order to suppress toxicity from polyQ species in Drosophila. According to additional studies, ataxin-3 does not rely on autophagy or the proteasome to suppress polyQ-dependent toxicity in fly eyes. Instead this deubiquitinase, through its interaction with Rad23, leads to increased protein levels of the co-chaperone DnaJ-1 and depends on it to protect against degeneration. Through DnaJ-1, our data connect ataxin-3 and Rad23 to protective processes involved with protein folding rather than increased turnover of toxic polyQ species.

PubMed ID
PubMed Central ID
PMC4710962 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Neurobiol. Disease
    Title
    Neurobiology of Disease
    Publication Year
    1994-
    ISBN/ISSN
    0969-9961
    Data From Reference
    Alleles (64)
    Genes (29)
    Human Disease Models (2)
    Natural transposons (1)
    Insertions (9)
    Experimental Tools (3)
    Transgenic Constructs (63)