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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Burke, Tara L. Miller, Jaime L. Grant, Patrick A. |
| Description | Author Affiliation: Burke TL ( From the Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, Virginia 22908.) |
| Abstract | Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease caused by polyglutamine (polyQ) expansion within the N-terminal region of the ataxin-7 protein, a known subunit of the SAGA complex. Although the mechanisms of SCA7 pathogenesis remain poorly understood, previous studies have shown perturbations in SAGA histone acetyltransferase function and transcriptional alterations. We sought to determine whether and how polyQ-expanded ataxin-7 affects SAGA catalytic activity. Here, we determined that polyQ-expanded ataxin-7 directly bound the Gcn5 catalytic core of SAGA while in association with its regulatory proteins, Ada2 and Ada3. This caused a significant decrease in Gcn5 histone acetyltransferase activity in vitro and in vivo at two SAGA-regulated galactose genes, GAL1 and GAL7. However, Gcn5 occupancy at the GAL1 and GAL7 promoters was increased in these cells, revealing a dominant-negative phenotype of the polyQ-expanded ataxin-7-incorporated, catalytically inactive SAGA. These findings suggest a dominant mechanism of polyQ-mediated SAGA inhibition that potentially contributes to SCA7 disease pathogenesis. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 47 |
| Volume Number | 288 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2013-11-22 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Nerve Tissue Proteins Chemistry Peptides P300-CBP Transcription Factors Adaptor Proteins, Signal Transducing Genetics Metabolism Ataxin-7 Galectins Histone Acetyltransferases Protein Structure, Tertiary Recombinant Proteins Saccharomyces Cerevisiae Enzymology Saccharomyces Cerevisiae Proteins Spinocerebellar Ataxias Transcription Factors Research Support, N.I.H., Extramural Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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