Differential protein acetylation induced by novel histone deacetylase inhibitors

被引：64

作者：

Glaser, KB ^{[1
]}

Li, J ^{[1
]}

Pease, LJ ^{[1
]}

Staver, MJ ^{[1
]}

Marcotte, PA ^{[1
]}

Guo, J ^{[1
]}

Frey, RR ^{[1
]}

Garland, RB ^{[1
]}

Heyman, HR ^{[1
]}

Wada, CK ^{[1
]}

Vasudevan, A ^{[1
]}

Michaelides, MR ^{[1
]}

Davidsen, SK ^{[1
]}

Curtin, ML ^{[1
]}

机构：

[1] Abbott Labs, Glogal Pharmaceut Res & Dev, Canc Res, Abbott Pk, IL 60064 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2004年 / 325卷 / 03期

关键词：

histone deacetylase; trichostatin A; acetylated tubulin; acetylated histones; suberoylanilide hydroxamic acid; tubulin deacetylase; chromatin remodeling; isozyme selectivity;

D O I：

10.1016/j.bbrc.2004.10.082

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Historic deacetylase (HDAC) inhibitors induce the hyperacetylation of nucleosomal histones in carcinoma cells resulting in the expression of repressed genes that cause growth arrest, terminal differentiation, and/or apoptosis. In vitro selectivity of several novel hydroxamate HDAC inhibitors including succinimide macrocyclic hydroxamates and the non-hydroxamate alpha-ketoamide inhibitors was investigated using isolated enzyme preparations and cellular assays. In vitro selectivity for the HDAC isozymes (HDAC1/2, 3, 4/3, and 6) was not observed for these HDAC inhibitors or the reference HDAC inhibitors, MS-275 and SAHA. In T24 andHCT1 16 cells these compounds caused the accumulation of acetylated histones H3 and H4; however, the succinimide macrocyclic hydroxamates and the alpha-ketoamides did not cause the accumulation of acetylated a-tubulin. These data suggest "selectivity" can be observed at the cellular level with HDAC inhibitors and that the nature of the zinc-chelating moiety is an important determinant of activity against tubulin deacetylase. (C) 2004 Elsevier Inc. All rights reserved.

引用

页码：683 / 690

页数：8

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