Histone acetylation/deacetylation and cancer: an "open" and "shut" case?
DNA in eukaryotic cells is packaged into chromatin. The main packaging component of chromatin is the nucleosome, and this is composed of proteins known as histones. Histones can be reversibly modified in several ways, and the best characterized of these modifications is histone acetylation. This is a reversible modification, which is carried out by two families of enzymes, the histone acetyltransferases (HATs), and the histone deacetylases (HDACs). These enzymes have important activities in many cellular processes including transcription, DNA replication and cell cycle progression. The mechanisms underlying tumor formation are multifaceted, and often involve mutations or alterations of genes involved with the regulation and control of the cell cycle or cell death. Because of their important roles in the regulation of such events, enzymes that affect histone acetylation status are increasingly being associated with tumors. This article describes some of the current knowledge about histone acetyltransferases and histone deacetylases, and how their multitudinal roles in cellular events may have important roles in tumorigensis.
Gray
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Van Andel Research Institute, Grand Rapids, MI 49503, USA. Steven.Gray@vai.org
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D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D019175:DNA Methylation; D004260:DNA Repair / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D016147:Genes, Tumor Suppressor; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D009369:Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D009858:Oncogenic Viruses / Q000472:pathogenicity; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D006657:Histones; D016160:Retinoblastoma Protein; D029701:Saccharomyces cerevisiae Proteins; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases; D006655:Histone Deacetylases