Abstract
SCA7 (spinocerebellar ataxia type 7) is a neurodegenerative disorder caused by a CAG repeat expansion in the SCA7 gene that leads to elongation of a polyglutamine tract in ataxin-7, a protein of unknown function. Sgf73, a putative yeast orthologue of ataxin-7, has been identified as a new component of the yeast SAGA (Spt/Ada/Gcn5 acetyltransferase) multisubunit complex, a co-activator required for the transcription of a subset of RNA polymerase II-dependent genes. We show here that ataxin-7 is an integral component of mammalian SAGA-like complexes, i.e. the TFTC [TBP (TATA-binding protein)-free TAF (TBP-associated factor) complex] and the STAGA (SPT3/TAF9/GCN5 acetyltransferase) complex. In agreement with this, immunoprecipitation of ataxin-7 retained a histone acetyltransferase activity characteristic of TFTC-like complexes. Moreover, polyglutamine expansion in ataxin-7 did not affect its incorporation into TFTCs/STAGA complexes purified from cells from a SCA7 patient. We demonstrate here that ataxin-7 is the human orthologue of a the yeast SAGA Sgf73 subunit, and is a bona fide subunit of human TFTC-like transcriptional complexes.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Ataxin-7
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Cell Cycle Proteins / chemistry*
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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HeLa Cells
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Histone Acetyltransferases / chemistry*
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Histone Acetyltransferases / genetics
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Histone Acetyltransferases / metabolism*
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Humans
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Multiprotein Complexes
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Nerve Tissue Proteins / chemistry*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Peptides / chemistry
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Peptides / genetics
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Protein Subunits
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Spinocerebellar Ataxias / etiology
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Spinocerebellar Ataxias / genetics
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Spinocerebellar Ataxias / metabolism
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / chemistry*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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p300-CBP Transcription Factors
Substances
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ATXN7 protein, human
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Ataxin-7
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Cell Cycle Proteins
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Multiprotein Complexes
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Nerve Tissue Proteins
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Peptides
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Protein Subunits
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SAGA complex, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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Transcription Factors
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polyglutamine
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Histone Acetyltransferases
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p300-CBP Transcription Factors
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p300-CBP-associated factor