Histone deacetylase inhibitors selectively suppress expression of HDAC7.

Histone deacetylase inhibitors selectively suppress expression of HDAC7. Research Abstract Details 

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Histone deacetylase inhibitors selectively suppress expression of HDAC7. Abstract Text:

Milos Dokmanovic,Gisela Perez,Weisheng Xu,Lang Ngo,Cathy Clarke,Raphael B Parmigiani,Paul A Marks,

There are 18 histone deacetylases (HDAC) generally divided into four classes based on homology to yeast HDACs. HDACs have many protein substrates in addition to histones that are involved in regulation of gene expression, cell proliferation, and cell death. Inhibition of HDACs can cause accumulation of acetylated forms of these proteins, thus altering their function. HDAC inhibitors (HDACi), such as the hydroxamic acid-based vorinostat (suberoylanilide hydroxamic acid), inhibit the zinc-containing classes I, II, and IV, but not the NAD(+)-dependent class III, enzymes. HDACis are a group of novel anticancer agents. Vorinostat is the first HDACi approved for clinical use in the treatment of the cancer cutaneous T-cell lymphoma. Factors affecting expression of HDACs are not well understood. This study focuses on the effect of the HDACi vorinostat on the expression of class I and class II HDACs. We found that vorinostat selectively down-regulates HDAC7 with little or no effect on the expression of other class I or class II HDACs. Fourteen cell lines were examined, including normal, immortalized, genetically transformed, and human cancer-derived cell lines. Down-regulation of HDAC7 by vorinostat is more pronounced in transformed cells sensitive to inhibitor-induced cell death than in normal cells or cancer cells resistant to induced cell death. Modulation of HDAC7 levels by small interfering RNA-mediated knockdown or by HDAC7 overexpression is associated with growth arrest but without detectable changes in acetylation of histones or p21 gene expression. Selective down-regulation of HDAC7 protein may serve as a marker of response of tumors to HDACi.

Histone deacetylase inhibitors selectively suppress expression of HDAC7. Publishing Authors By Initials

M Dokmanovic,G Perez,W Xu,L Ngo,C Clarke,RB Parmigiani,PA Marks,

For similar integumentary system: skin research abstracts see: integumentary system: skin research

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Histone deacetylase inhibitors selectively suppress expression of HDAC7. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Molecular cancer therapeutics

VOLUME: 6

Page Numbers: 2525-34

Journal Abbreviation: Mol. Cancer Ther.

ISSN: 1535-7163

DAY: 27

MONTH: Sep

YEAR: 2007

Histone deacetylase inhibitors selectively suppress expression of HDAC7. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 101132535

Histone deacetylase inhibitors selectively suppress expression of HDAC7. Keywords Mesh Terms:

KEYWORDS: Skin

MESH TERMS: enzymology

Chemical & Substance for Abstract: Histone deacetylase inhibitors selectively suppress expression of HDAC7. Information

Substance Name: Histone Deacetylases

Registry Number: EC 3.5.1.-

Grant and Affiliation Information for Histone deacetylase inhibitors selectively suppress expression of HDAC7.

AFFILIATION: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

Country: United States

AGENCY: United States NCI

GRANT: P30CA-08748-41

ACRONYM: CA

MEDLINETA: Mol Cancer Ther

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