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Lam, Y.C., Bowman, A.B., Jafar-Nejad, P., Lim, J., Richman, R., Fryer, J.D., Hyun, E.D., Duvick, L.A., Orr, H.T., Botas, J., Zoghbi, H.Y. (2006). ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology.  Cell 127(7): 1335--1347.
FlyBase ID
FBrf0193611
Publication Type
Research paper
Abstract

Spinocerebellar ataxia type 1 (SCA1) is one of several neurodegenerative diseases caused by expansion of a polyglutamine tract in the disease protein, in this case, ATAXIN-1 (ATXN1). A key question in the field is whether neurotoxicity is mediated by aberrant, novel interactions with the expanded protein or whether its wild-type functions are augmented to a deleterious degree. We examined soluble protein complexes from mouse cerebellum and found that the majority of wild-type and expanded ATXN1 assembles into large stable complexes containing the transcriptional repressor Capicua. ATXN1 directly binds Capicua and modulates Capicua repressor activity in Drosophila and mammalian cells, and its loss decreases the steady-state level of Capicua. Interestingly, the S776A mutation, which abrogates the neurotoxicity of expanded ATXN1, substantially reduces the association of mutant ATXN1 with Capicua in vivo. These data provide insight into the function of ATXN1 and suggest that SCA1 neuropathology depends on native, not novel, protein interactions.

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Related Publication(s)
Note

Hosting neurotoxicity in polyglutamine disease.
Liu and Bonini, 2006, Cell 127(7): 1299--1300 [FBrf0195122]

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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell
    Title
    Cell
    Publication Year
    1974-
    ISBN/ISSN
    0092-8674
    Data From Reference
    Alleles (10)
    Genes (8)
    Human Disease Models (1)
    Natural transposons (1)
    Insertions (5)
    Experimental Tools (1)
    Transgenic Constructs (5)