Identification and characterization of Sir2 inhibitors through phenotypic assays in yeast.
Comb Chem High Throughput Screen
; 7(7): 661-8, 2004 Nov.
Article
em En
| MEDLINE
| ID: mdl-15578928
ABSTRACT
Yeast Sir2 is a defining member of a large family of protein deacetylases found in organisms ranging from bacteria to humans. SIR2 was discovered as a gene required for mating in S. cerevisiae 25 years ago, but it was only recently that Sir2's activity as an NAD-dependent protein deacetylase was established. However, years of extensive research did generate a large body of knowledge about the cellular roles of Sir2 in yeast long before its biochemical function was discovered. In addition to Sir2, yeast have four additional NAD-dependent histone deacetylases Hst1-4 (for homologue of Sir2), with distinct cellular roles. Detailed knowledge of the phenotypes of SIR2 and HST loss of function mutants has allowed design of a series of cell based screens that yielded the first inhibitors of NAD-dependent protein deacetylases. These phenotypic assays, amenable to high throughput screening, and coupled with transcript array analysis for evaluation of compound specificity, allowed the identification and detailed characterization of a series of Sir2 inhibitors, entirely bypassing traditional biochemical approaches.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Leveduras
/
Sirtuínas
/
Proteínas Reguladoras de Informação Silenciosa de Saccharomyces cerevisiae
/
Inibidores de Histona Desacetilases
/
Histona Desacetilases
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Comb Chem High Throughput Screen
Assunto da revista:
BIOLOGIA MOLECULAR
/
QUIMICA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Estados Unidos