1. Academic Validation
  2. Identification of a small molecule inhibitor of Sir2p

Identification of a small molecule inhibitor of Sir2p

  • Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15113-8. doi: 10.1073/pnas.261574398.
A Bedalov 1 T Gatbonton W P Irvine D E Gottschling J A Simon
Affiliations

Affiliation

  • 1 Divisions of Clinical Research, Basic Sciences, and Human Biology, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA.
Abstract

Sir2p is an NAD(+)-dependent histone deacetylase required for chromatin-dependent silencing in yeast. In a cell-based screen for inhibitors of Sir2p, we identified a compound, splitomicin, that creates a conditional phenocopy of a sir2 deletion mutant in Saccharomyces cerevisiae. Cells grown in the presence of the drug have silencing defects at telomeres, silent mating-type loci, and the ribosomal DNA. In addition, whole genome microarray experiments show that splitomicin selectively inhibits Sir2p. In vitro, splitomicin inhibits NAD(+)-dependent histone deacetylase activity (HDA) of the Sir2 protein. Mutations in SIR2 that confer resistance to the drug map to the likely acetylated histone tail binding domain of the protein. By using splitomicin as a chemical genetic probe, we demonstrate that continuous HDA of Sir2p is required for maintaining a silenced state in nondividing cells.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-100585
    98.42%, Sir2p 抑制剂