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
Reads0
Chats0
TLDR
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.Abstract:
Transcriptional regulation in eukaryotes occurs within a chromatin setting, and is strongly influenced by the post-translational modification of histones, the building blocks of chromatin, such as methylation, phosphorylation and acetylation. Acetylation is probably the best understood of these modifications: hyperacetylation leads to an increase in the expression of particular genes, and hypoacetylation has the opposite effect. Many studies have identified several large, multisubunit enzyme complexes that are responsible for the targeted deacetylation of histones. The aim of this review is to give 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. SAGE (serial analysis of gene expression) data show that HDACs are generally expressed in almost all tissues investigated. Surprisingly, no major differences were observed between the expression pattern in normal and malignant tissues. However, significant variation in HDAC expression was observed within tissue types. HDAC inhibitors have been shown to induce specific changes in gene expression and to influence a variety of other processes, including growth arrest, differentiation, cytotoxicity and induction of apoptosis. This challenging field has generated many fascinating results which will ultimately lead to a better understanding of the mechanism of gene transcription as a whole.read more
Citations
More filters
Journal ArticleDOI
Tumour necrosis factor‐α depletes histone deacetylase 1 protein through IKK2
TL;DR: This study found that cells treated with the pro‐inflammatory cytokine tumour necrosis factor‐α rapidly and substantially reduced HDAC1 protein levels without affecting other class I HDACs.
Journal ArticleDOI
HDAC6 and ovarian cancer.
Joshua Haakenson,Xiaohong Zhang +1 more
TL;DR: The idea of usingHDAC6 as a target for cancer treatment continues to expand in recent years, and more potent and specific HDAC6 inhibitors are required to effectively down-regulate the tumor-prone cell signaling pathways responsible for ovarian cancer.
Journal ArticleDOI
Proteomic analyses of intermediate filaments reveals cytokeratin8 is highly acetylated – implications for colorectal epithelial homeostasis
Siân H. Leech,Caroline A. Evans,Leila Shaw,Chi H. Wong,Joanne B. Connolly,John R. Griffiths,Anthony D. Whetton,Bernard M. Corfe +7 more
TL;DR: It is reported that CKs are highly acetylated in a colon cancer cell line, with five acetylation sites characterised on CK8 and a further one on CK18, which indicates a novel action of butyrate as a cancer preventive agent.
Journal ArticleDOI
Dual-Mode HDAC Prodrug for Covalent Modification and Subsequent Inhibitor Release.
Kevin B. Daniel,Eric D. Sullivan,Yao Chen,Joshua C. Chan,Patricia A. Jennings,Carol A. Fierke,Seth M. Cohen +6 more
TL;DR: An original prodrug design with a dual mode of action for HDAC inhibition, developed by appending a promoiety, sensitive to thiols, to the hydroxamic acid warhead (termed SAHA-TAP), demonstrates cytotoxicity activity against various cancer cell lines.
Journal ArticleDOI
Screening of selective histone deacetylase inhibitors by proteochemometric modeling
Dingfeng Wu,Qi Huang,Yida Zhang,Qingchen Zhang,Qi Liu,Jun Gao,Jun Gao,Zhiwei Cao,Ruixin Zhu,Ruixin Zhu +9 more
TL;DR: A best PCM model based on protein structure similarity descriptors and 32-dimensional general descriptors was derived, which shows a powerful ability to screen selective HDAC inhibitors and provides a potential way to discover or design novel candidate antitumor drugs with reduced side effect.
References
More filters
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
The fundamental role of epigenetic events in cancer
Peter A. Jones,Stephen B. Baylin +1 more
TL;DR: This review discusses patterns of DNA methylation and chromatin structure in neoplasia and the molecular alterations that might cause them and/or underlie altered gene expression in cancer.
Journal ArticleDOI
HDAC6 is a microtubule-associated deacetylase
Charlotte Hubbert,Amaris Guardiola,Rong Shao,Yoshiharu Kawaguchi,Akihiro Ito,Andrew B. Nixon,Minoru Yoshida,Xiao-Fan Wang,Tso-Pang Yao +8 more
TL;DR: The results show that HDAC6 is the tubulin deacetylase, and provide evidence that reversible acetylation regulates important biological processes beyond histone metabolism and gene transcription, including microtubule-dependent cell motility.
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
TL;DR: 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.
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.