Journal ArticleDOI
Histone deacetylases and cancer: causes and therapies.
Paul A. Marks,Richard A. Rifkind,Victoria M. Richon,Ronald Breslow,Thomas E. Miller,William Kevin Kelly +5 more
TLDR
Together, histone acetyltransferases and histone deacetylases determine the acetylation status of histones, and inhibitors of HDACs have been found to cause growth arrest, differentiation and/or apoptosis of many tumours cells by altering the transcription of a small number of genes.Abstract:
Together, histone acetyltransferases and histone deacetylases (HDACs) determine the acetylation status of histones. This acetylation affects the regulation of gene expression, and inhibitors of HDACs have been found to cause growth arrest, differentiation and/or apoptosis of many tumours cells by altering the transcription of a small number of genes. HDAC inhibitors are proving to be an exciting therapeutic approach to cancer, but how do they exert this effect?read more
Citations
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The epigenomics of cancer.
Peter A. Jones,Stephen B. Baylin +1 more
TL;DR: Recent advances in understanding how epigenetic alterations participate in the earliest stages of neoplasia, including stem/precursor cell contributions, are reviewed and the growing implications of these advances for strategies to control cancer are discussed.
Journal ArticleDOI
Gene Silencing in Cancer in Association with Promoter Hypermethylation
TL;DR: The mechanisms of gene silencing in cancer and clinical applications of this phenomenon are reviewed, especially tumor-suppressor genes.
Journal ArticleDOI
Histone deacetylases (HDACs): characterization of the classical HDAC family
Annemieke J.M. de Ruijter,Albert H. van Gennip,Huib N. Caron,Stephan Kemp,André B.P. van Kuilenburg +4 more
TL;DR: In this paper, a comprehensive overview of the structure, function and tissue distribution of members of the classical histone deacetylase (HDAC) family, in order to gain insight into the regulation of gene expression through HDAC activity is presented.
Journal ArticleDOI
Anticancer activities of histone deacetylase inhibitors.
TL;DR: Recent advances in the understanding of the molecular events that underlie the anticancer effects of HDAC inhibitors are summarized and how such information could be used in optimizing the development and application of these agents in the clinic, either as monotherapies or in combination with other anticancer drugs are discussed.
Journal ArticleDOI
Modulation of NF-κB-dependent transcription and cell survival by the SIRT1 deacetylase
Fan Yeung,Jamie E. Hoberg,Catherine S. Ramsey,Michael D Keller,David R. Jones,Roy A. Frye,Marty W. Mayo +6 more
TL;DR: It is demonstrated that SIRT1, a nicotinamide adenosine dinucleotide‐dependent histone deacetylase, regulates the transcriptional activity of NF‐κB and activity augments apoptosis in response to TNFα.
References
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Journal ArticleDOI
The language of covalent histone modifications.
Brian D. Strahl,C D Allis +1 more
TL;DR: It is proposed that distinct histone modifications, on one or more tails, act sequentially or in combination to form a ‘histone code’ that is, read by other proteins to bring about distinct downstream events.
Journal ArticleDOI
Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A.
TL;DR: Results clearly indicate that TSA is a potent and specific inhibitor of the histone deacetylase and that the in vivo effect of TSA on cell proliferation and differentiation can be attributed to the inhibition of the enzyme.
Journal ArticleDOI
Twenty-Five Years of the Nucleosome, Fundamental Particle of the Eukaryote Chromosome
Roger D. Kornberg,Yahli Lorch +1 more
TL;DR: The chromatin field needs much more information about structure beyond the nucleosome, and there is insufficient evidence that acetylation actually causes chromatin unfolding, and functional analysis in cell-free systems must be extended beyond theucleosome to the chromosomal context.
Journal ArticleDOI
Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors.
Michael S. Finnin,Jill R. Donigian,Alona Cohen,Victoria M. Richon,Richard A. Rifkind,Paul A. Marks,Ronald Breslow,Nikola P. Pavletich +7 more
TL;DR: The structure of the histone deacetylase catalytic core is described, as revealed by the crystal structure of a homologue from the hyperthermophilic bacterium Aquifex aeolicus, and it is established that the residues that make up the active site and contact the inhibitors are conserved across the HDAC family.
Journal ArticleDOI
Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen
Christopher J. Phiel,Fang Zhang,Eric Y. Huang,Matthew G. Guenther,Mitchell A. Lazar,Peter S. Klein +5 more
TL;DR: It is proposed that inhibition of histone deacetylase provides a mechanism for valproic acid-induced birth defects and could also explain the efficacy of valproIC acid in the treatment of bipolar disorder.