Tumour necrosis factor-α depletes histone deacetylase 1 protein through IKK2

被引：30

作者：

Y N Vashisht Gopal ^{[1
]}

Tarandeep S Arora ^{[1
]}

Michael W Van Dyke ^{[1
]}

机构：

[1] Department of Molecular and Cellular Oncology, UT M.D. Anderson Cancer Center, Houston

来源：

The EMBO Reports | 2006年 / 7卷 / 3期

关键词：

Chromatin; Histone deacetylases; IKK2; NF-kB; TNF-α;

D O I：

10.1038/sj.embor.7400613

中图分类号：

学科分类号：

摘要：

Class I histone deacetylases (HDACs) are ubiquitous enzymes that repress gene expression by deacetylating histone tails and promoting chromatin compaction. Pro-inflammatory agents activate programmes of gene expression through transcription factors such as nuclear factor-κB (NF-κB), even in the context of ubiquitous HDAC activity. How this is accomplished remains unknown. We 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. In addition, HDAC1 depletion occurred through protein degradation, required IKK2 activity and resulted in increased transcription from both NF-κB-associated and unassociated gene promoters. Our study suggests that the activation of programmes of gene expression by pro-inflammatory agents requires global changes in specific critical epigenetic regulators such as HDAC1. © 2006 European Molecular Biology Organization.

引用

页码：291 / 296

页数：5

共 13 条

[1]

Baek S.H., Ohgi K.A., Rose D.W., Koo E.H., Glass C.K., Rosenfeld M.G., Exchange of N-CoR corepressor and Tip60 coactivator complexes links gene expression by NF-κB and b-amyloid precursor protein, Cell, 110, pp. 55-67, (2002)

[2]

Blanchard F., Chipoy C., Histone deacetylase inhibitors: New drugs for the treatment of inflammatory diseases?, Drug Discov Today, 10, pp. 197-204, (2005)

[3]

Cheung W.L., Briggs S.D., Allis C.D., Acetylation and chromosomal functions, Curr Opin Cell Biol, 12, pp. 326-333, (2000)

[4]

de Ruijter A.J., van Gennip A.H., Caron H.N., Kemp S., van Kuilenburg A.B., Histone deacetylases (HDACs): Characterization of the classical HDAC family, Biochem J, 370, pp. 737-749, (2003)

[5]

El-Deiry W.S., Tokino T., Velculescu V.E., Levy D.B., Parsons R., Trent J.M., Lin D., Mercer W.E., Kinzler K.W., Vogelstein B., WAF1, a potential mediator of p53 tumor suppression, Cell, 75, pp. 817-825, (1993)

[6]

Finnberg N., El-Deiry W.S., Activating FOXO3a, NF-κB and p53 by targeting IKKs: An effective multi-faceted targeting of the tumor-cell phenotype?, Cancer Biol Ther, 3, pp. 614-616, (2004)

[7]

Ghosh S., May M.J., Kopp E.B., NF-κB and Rel proteins: Evolutionarily conserved mediators of immune responses, Annu Rev Immunol, 16, pp. 225-260, (1998)

[8]

Glaser K.B., Staver M.J., Waring J.F., Stender J., Ulrich R.G., Davidsen S.K., Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: Defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines, Mol Cancer Ther, 2, pp. 151-163, (2003)

[9]

Lagger G., Et al., Essential function of histone deacetylase 1 in proliferation control and CDK inhibitor repression, EMBO J, 21, pp. 2672-2681, (2002)

[10]

Li Q., Verma I.M., NF-κB regulation in the immune system, Nat Rev Immunol, 2, pp. 725-734, (2002)

← 1 2 →