The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Identification of a small molecule inhibitor of Sir2p
Open accessAbstract
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.
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Cites
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Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase
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hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase
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Negative Control of p53 by Sir2α Promotes Cell Survival under Stress
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A Mammalian Histone Deacetylase Related to the Yeast Transcriptional Regulator Rpd3p
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Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans
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Phylogenetic classification of prokaryotic and eukaryotic Sir2-like proteins
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Position effect at S. cerevisiae telomeres: Reversible repression of Pol II transcription
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Self-citation
Cited by
Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase
Yeung, F., Hoberg, J. E., Ramsey, C. S., Keller, M. D., Jones, D. R., Frye, R. A., & Mayo, M. W. (2004) · The EMBO Journal · doi:10.1038/sj.emboj.7600244 · Cited by 2,750
Cancer epigenetics reaches mainstream oncology
Rodríguez-Paredes, M., & Esteller, M. (2011) · Nature Medicine · doi:10.1038/nm.2305 · Cited by 1,205
Mechanism of Human SIRT1 Activation by Resveratrol
Borra, M. T., Smith, B. C., & Denu, J. M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501250200 · Cited by 1,065
Bitterman, K. J., Anderson, R. M., Cohen, H. Y., Latorre-Esteves, M., & Sinclair, D. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m205670200 · Cited by 1,002
Sauve, A. A., Wolberger, C., Schramm, V. L., & Boeke, J. D. (2006) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.74.082803.133500 · Cited by 763
Metadata
- Authors
- Bedalov, A., Gatbonton, T., Irvine, W. P., Gottschling, D. E., & Simon, J. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-12-18
- Volume
- 98
- Issue
- 26
- Pages
- 15113-15118
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2149703257
- Cited by
- 346
- References
- 47
- FWCI
- 7.81
- Type
- journal article
- Language
- en
- Open access
- green
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- Bedalov, A., Gatbonton, T., Irvine, W. P., Gottschling, D. E., & Simon, J. A. (2001). Identification of a small molecule inhibitor of Sir2p. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.261574398
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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