Polyglutamine-expanded spinocerebellar ataxia-7 protein disrupts normal SAGA and SLIK histone acetyltransferase activity.
Proc Natl Acad Sci U S A
; 102(24): 8478-82, 2005 Jun 14.
Article
em En
| MEDLINE
| ID: mdl-15932941
ABSTRACT
Histone acetyltransferases have been shown to participate in many essential cellular processes, particularly those associated with activation of transcription. SAGA (Spt-Ada-Gcn5 acetyltransferase) and SLIK (SAGA-like) are two highly homologous multisubunit histone acetyltransferase complexes that were originally identified in the yeast Saccharomyces cerevisiae. Here, we identify the protein Sgf73/Sca7 as a component of SAGA and SLIK, and a homologue of the human SCA7-encoded protein ataxin-7, which, in its polyglutamine expanded pathological form, is responsible for the neurodegenerative disease spinocerebellar ataxia 7 (SCA7). Our findings indicate that yeast Sca7 is necessary for the integrity and function of both SAGA and SLIK, and that the human ataxin-7 is able to compliment the loss of Sca7 in yeast. A polyglutamine-expanded version of ataxin-7 assembles a SAGA complex that is depleted of critical proteins that regulate the ability of SAGA to acetylate nucleosomes. These observations have significant implications for the function of the human Sca7 protein in disease pathogenesis.
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1
Base de dados:
MEDLINE
Assunto principal:
Acetiltransferases
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Leveduras
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Expansão das Repetições de Trinucleotídeos
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Complexos Multiproteicos
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Proteínas do Tecido Nervoso
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article