The mechanism of the anti-tumor activity of the histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA).
Histone deacetylases (HDAC) are ubiquitously distributed through chromatin. Nevertheless HDAC inhibitors (HDACi), such as SAHA, selectively alter the transcription of as few as 2-5% of expressed genes in various transformed cells. p21(WAF1) is one of the most commonly induced genes in cells cultured with SAHA. Understanding the mechanism of the selective effects of the HDACi is a challenging problem. Gui et al. have identified effects of SAHA on p21(WAF1) promotor associated proteins that explain, at least in part, the selective effects of HDAC in altering gene expression.
Marks
Paul A
PA
Memorial Sloan-Kettering Cancer Center, New York City, New York 10021, USA. PaulA_Marks@mskcc.org
D000970:Antineoplastic Agents / Q000378:metabolism*; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic; D000077337:Vorinostat
D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat; D006655:Histone Deacetylases