Histone deacetylase inhibitor apicidin induces cyclin E expression through Sp1 sites

doi:10.1016/j.bbrc.2006.02.081

Biochemical and Biophysical Research Communications

Volume 342, Issue 4, 21 April 2006, Pages 1168-1173

https://doi.org/10.1016/j.bbrc.2006.02.081 Get rights and content

Abstract

We show that a histone deacetylase (HDAC) inhibitor apicidin increases the transcriptional activity of cyclin E gene, which results in accumulation of cyclin E mRNA and protein in a time- and dose-dependent manner. Interestingly, apicidin induction of cyclin E gene is found to be mediated by Sp1- rather than E2F-binding sites in the cyclin E promoter, as evidenced by the fact that specific inhibition of Sp1 leads to a decrease in apicidin activation of cyclin E promoter activity and protein expression, but mutation of E2F-binding sites of cyclin E promoter region fails to inhibit the ability of apicidin to activate cyclin E transcription. In addition, this transcriptional activation of cyclin E by apicidin is associated with histone hyperacetylation of cyclin E promoter region containing Sp1-binding sites. Our results demonstrate that regulation of histone modification by an HDAC inhibitor apicidin contributes to induction of cyclin E expression and this effect is Sp1-dependent.

Section snippets

Materials and methods

Cell culture and reagents. Human cervix cancer cell line HeLa was cultured in Dulbecco’s modified Eagle’s medium (Life Technologies, Gaithersburg, MD), supplemented with 10% fetal bovine serum (HyClone Laboratories, Logan, UT), and 1% penicillin/streptomycin (Life Technologies). Apicidin, (cyclo(N-O-methyl-l-tryptophanyl-l-isoleucinyl-d-pipecolinyl-l-2-amino-8- oxodecanoyl)), was prepared from Fusarium species Strain KCTC 16677, according to the method previously described [18]. Trichostatin A

Results and discussion

Since HDAC inhibitors such as trapoxin or oxamflatin have been shown to induce cyclin E expression [20], [21], we first examined the effect of apicidin on the protein expression of cyclin E in HeLa cells. As shown in Figs. 1A and B, apicidin induced expression of cyclin E protein in a time- and dose-dependent manner. We next analyzed the changes of cyclin E mRNA levels in response to apicidin treatment. Apicidin resulted in a time-dependent induction of cyclin E mRNA: apicidin-induced cyclin E

Acknowledgment

This work was supported by Grant No. 2003-041-E00317 from the Korea Research Foundation.

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¹: These authors contributed equally to this work.

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Histone deacetylase inhibitor apicidin induces cyclin E expression through Sp1 sites

Abstract

Section snippets

Materials and methods

Results and discussion

Acknowledgment

Cell

Gene

Exp. Cell Res.

J. Biol. Chem.

Exp. Cell Res.

J. Biol. Chem.

Gene

J. Biol. Chem.

J. Biol. Chem.

Curr. Opin. Genet. Dev.

Principles of CDK regulation

Nature

Mechanism of active transcriptional repression by the retinoblastoma protein

Nature

The language of covalent histone modifications

Nature