Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

UbcH6 is a member of an evolutionally conserved subfamily of E2 ubiquitin-conjugating enzymes. In this study, we report that UbcH6 interacts with and ubiquitinates ataxin-1, the spinocerebellar ataxia type 1 gene product. UbcH6 was identified as an ataxin-1-interacting protein using a yeast two-hybrid screen. UbcH6 co-immunoprecipitates and co-localizes with the ataxin-1 protein in the nucleus. Our binding assays showed that ataxin-1 interacts with UbcH6 through its AXH domain. Interestingly, UbcH6 could ubiquitinate ataxin-1 in the absence of an E3 ligase. The expression level of UbcH6 regulated the rate of ataxin-1 degradation. This study demonstrates that UbcH6 and ataxin-1 are E2-substrate cognate pairs in the ubiquitin-proteasome system.
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PMID:UbcH6 interacts with and ubiquitinates the SCA1 gene product ataxin-1. 1843 7

Spinocerebellar ataxia type 1 (SCA1) is an autosomal-dominant neurodegenerative disorder characterized by ataxia and progressive motor deterioration. SCA1 is caused by expansion of the polyglutamine tract in the SCA1 gene product, ataxin-1. We previously reported that the E2 ubiquitin-conjugating enzyme UbcH6 interacts with and ubiquitinates the ataxin-1 proteins as an E2-substrate cognate pair in the ubiquitin-proteasome system. In the present study, we further investigated whether the function of ataxin-1 is associated with UbcH6 and found that UbcH6 regulates the transcriptional repression activity of ataxin-1. The overexpression of UbcH6 reduced the transcriptional repression activity of ataxin-1. Interestingly, ataxin-1(30Q) was more affected by the presence of UbcH6 than ataxin-1(82Q), implying that the length of the polyglutamine tract in ataxin-1 might be involved in determining the stability of ataxin-1. The half-life of ataxin-1(82Q) was longer than that of ataxin-1(30Q) in the presence of UbcH6. shRNAs targeting UbcH6 enhanced the transcriptional repression activity of ataxin-1. In addition, the overexpression of UbcH6 reduced the formation of ataxin-1 aggregates. Our studies demonstrate that UbcH6 modulates the transcriptional repression activity of ataxin-1 by modulating the degradation of ataxin-1, suggesting that UbcH6 may have some therapeutic potential in the treatment of SCA1.
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PMID:The ubiquitin-conjugating enzyme UbcH6 regulates the transcriptional repression activity of the SCA1 gene product ataxin-1. 1851 31