Sp1 and TAFII130 transcriptional activity disrupted in early Huntington's disease.
Science
; 296(5576): 2238-43, 2002 Jun 21.
Article
em En
| MEDLINE
| ID: mdl-11988536
ABSTRACT
Huntington's disease (HD) is an inherited neurodegenerative disease caused by expansion of a polyglutamine tract in the huntingtin protein. Transcriptional dysregulation has been implicated in HD pathogenesis. Here, we report that huntingtin interacts with the transcriptional activator Sp1 and coactivator TAFII130. Coexpression of Sp1 and TAFII130 in cultured striatal cells from wild-type and HD transgenic mice reverses the transcriptional inhibition of the dopamine D2 receptor gene caused by mutant huntingtin, as well as protects neurons from huntingtin-induced cellular toxicity. Furthermore, soluble mutant huntingtin inhibits Sp1 binding to DNA in postmortem brain tissues of both presymptomatic and affected HD patients. Understanding these early molecular events in HD may provide an opportunity to interfere with the effects of mutant huntingtin before the development of disease symptoms.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Transcrição Gênica
/
DNA
/
Proteínas Nucleares
/
Fator de Transcrição Sp1
/
Doença de Huntington
/
Fatores Associados à Proteína de Ligação a TATA
/
Fator de Transcrição TFIID
/
Proteínas de Ligação a DNA
/
Proteínas do Tecido Nervoso
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article