The role of histone deacetylases (HDACs) in human cancer - PubMed (original) (raw)

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The role of histone deacetylases (HDACs) in human cancer

Santiago Ropero et al. Mol Oncol. 2007 Jun.

Abstract

The balance of histone acetylation and deacetylation is an epigenetic layer with a critical role in the regulation of gene expression. Histone acetylation induced by histone acetyl transferases (HATs) is associated with gene transcription, while histone hypoacetylation induced by histone deacetylase (HDAC) activity is associated with gene silencing. Altered expression and mutations of genes that encode HDACs have been linked to tumor development since they both induce the aberrant transcription of key genes regulating important cellular functions such as cell proliferation, cell-cycle regulation and apoptosis. Thus, HDACs are among the most promising therapeutic targets for cancer treatment, and they have inspired researchers to study and develop HDAC inhibitors.

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Figures

Figure 1

Figure 1

Different ways by which HDACs are recruited to gene promoters. An array of nucleosomes is shown. Histone octamers are represented by circles and the DNA is shown in red. Histone deacetylation induced by recruitment of HDAC to gene promoters by different factors including, DNA methyl transferases (DNMT), the methyl binding protein MeCP2, Estrogen receptor (ER) and transcription factors (E2F, Rb).

Figure 2

Figure 2

A model showing a possible effect of HDAC2 mutation in cancer development. class I HDACs are involved in gene transcription‐repression mediated by retinoblastoma protein. The lost of HDAC2 function could induce the hyperacetylation and reexpression of genes regulated by retinoblastoma protein Rb, and with crucial functions in cell cycle regulation.

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References

    1. Bai, S. , Ghoshal, K. , Datta, J. , Majumder, S. , Yoon, S.O. , Jacob, S.T. , 2005. DNA methyltransferase 3b regulates nerve growth factor-induced differentiation of PC12 cells by recruiting histone deacetylase 2. Mol. Cell Biol.. 25, 751–766. - PMC - PubMed
    1. Bouras, T. , Fu, M. , Sauve, A.A. , Wang, F. , Quong, A.A. , Perkins, N.D. , Hay, R.T. , Gu, W. , Pestell, R.G. , 2005. SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. J. Biol. Chem.. 280, 10264–10276. - PubMed
    1. Bradbury, C.A. , Khanim, F.L. , Hayden, R. , Bunce, C.M. , White, D.A. , Drayson, M.T. , Craddock, C. , Turner, B.M. , 2005. Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia. 19, 1751–1759. - PubMed
    1. Brehm, A. , Miska, E.A. , McCance, D.J. , Reid, J.L. , Bannister, A.J. , Kouzarides, T. , 1998. Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature. 391, 597–601. - PubMed
    1. Chen, W.Y. , Wang, D.H. , Yen, R.C. , Luo, J. , Gu, W. , Baylin, S.B. , 2005. Tumor suppressor HIC1 directly regulates SIRT1 to modulate p53-dependent DNA-damage responses. Cell. 123, 437–448. - PubMed

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