Histone deacetylase inhibitors: molecular mechanisms of action.

Histone deacetylase inhibitors: molecular mechanisms of action. Research Abstract Details 

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Histone deacetylase inhibitors: molecular mechanisms of action. Abstract Text:

W S Xu,R B Parmigiani,P A Marks,

This review focuses on the mechanisms of action of histone deacetylase (HDAC) inhibitors (HDACi), a group of recently discovered 'targeted' anticancer agents. There are 18 HDACs, which are generally divided into four classes, based on sequence homology to yeast counterparts. Classical HDACi such as the hydroxamic acid-based vorinostat (also known as SAHA and Zolinza) inhibits classes I, II and IV, but not the NAD+-dependent class III enzymes. In clinical trials, vorinostat has activity against hematologic and solid cancers at doses well tolerated by patients. In addition to histones, HDACs have many other protein substrates involved in regulation of gene expression, cell proliferation and cell death. Inhibition of HDACs causes accumulation of acetylated forms of these proteins, altering their function. Thus, HDACs are more properly called 'lysine deacetylases.' HDACi induces different phenotypes in various transformed cells, including growth arrest, activation of the extrinsic and/or intrinsic apoptotic pathways, autophagic cell death, reactive oxygen species (ROS)-induced cell death, mitotic cell death and senescence. In comparison, normal cells are relatively more resistant to HDACi-induced cell death. The plurality of mechanisms of HDACi-induced cell death reflects both the multiple substrates of HDACs and the heterogeneous patterns of molecular alterations present in different cancer cells.

Histone deacetylase inhibitors: molecular mechanisms of action. Publishing Authors By Initials

WS Xu,RB Parmigiani,PA Marks,

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: substrate specificity research

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Histone deacetylase inhibitors: molecular mechanisms of action. Journal Published:

PUBLICATION TYPE: Review

Journal: Oncogene

VOLUME: 26

Page Numbers: 5541-52

Journal Abbreviation: Oncogene

ISSN: 0950-9232

DAY: 13

MONTH: Aug

YEAR: 2007

Histone deacetylase inhibitors: molecular mechanisms of action. Information

Number of References: 115

LANGUAGE: eng

NlmUniqueID: 8711562

Histone deacetylase inhibitors: molecular mechanisms of action. Keywords Mesh Terms:

KEYWORDS: Substrate Specificity

MESH TERMS: enzymology

Chemical & Substance for Abstract: Histone deacetylase inhibitors: molecular mechanisms of action. Information

Substance Name: Histone Deacetylases

Registry Number: EC 3.5.1.-

Grant and Affiliation Information for Histone deacetylase inhibitors: molecular mechanisms of action.

AFFILIATION: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.

Country: England

AGENCY: United States NCI

GRANT: P30CA08748-41

ACRONYM: CA

MEDLINETA: Oncogene

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