Autor: |
Posakony, Jeff, Hirao, Maki, Bedalov, Antonio |
Zdroj: |
Combinatorial Chemistry & High Throughput Screening; November 2004, Vol. 7 Issue: 7 p661-668, 8p |
Abstrakt: |
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.XXXY YYZZZ |
Databáze: |
Supplemental Index |
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