Words similar to ataxin-
Example sentences for: ataxin-
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The major question now is whether there are analogous prion-like proteins in mammalian cells that are involved in aggregation of huntingtin or ataxin-3 and subsequent neurodegenerative disease.
Although the formation of intranuclear inclusions has not been observed in previous studies of Ras-related GTPases, it is a common feature of several neurodegenerative disorders where abnormal proteins containing poly-Gln tracts are synthesized as a result of CAG codon expansions [ 52 ] . Examples include Huntington's disease (huntingtin) [ 53 54 ] , spinocerebellar ataxia (SCA) types 1 and 3 (ataxin-1 and ataxin-3) [ 55 56 ] and dentatorubral-pallidoluysian atrophy (atrophin-1) [ 57 ] . These poly-Gln protein aggregates typically contain ubiquitin [ 58 ] and members of the Hsp70 chaperone family [ 59 ] , consistent with a proposed pathway for cellular clearance of toxic misfolded proteins.
Indeed, a similar explanation has been invoked to explain the presence of Hsp70 and ubiquitin in nuclear aggregates observed in cells expressing abnormal gene products with poly-Gln tracts, such as huntingtin [ 54 ] and ataxin-1 [ 59 ] . Based on reports that overexpression of chaperones [ 59 62 ] or a dominant-negative form of the ubiquitin-conjugating enzyme [ 63 ] can suppress the formation of poly-Gln protein aggregates, Kaytor and Warren [ 58 ] proposed a three-stage model wherein (i) molecular chaperones initially associate with the misfolded protein, (ii) failure to diminish the pool of misfolded protein leads to aggregation and ubiquitination and (iii) inefficient degradation of the aggregate by the proteasome is manifested by the accumulation of inclusion bodies.
For example, recent experiments demonstrated that [RNQ + ] prion dramatically stimulated aggregation of fragments of recombinant human huntingtin or ataxin-3 with an expanded polyQ domain cloned in yeast (Osherovich and Weissman 2001; Meriin et al.
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