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Transcriptional activation of p21(WAF1/CIP1) by apicidin, a novel histone deacetylase inhibitor.

Authors
  • Kim, J S
  • Lee, S
  • Lee, T
  • Lee, Y W
  • Trepel, J B
Type
Published Article
Journal
Biochemical and biophysical research communications
Publication Date
Mar 09, 2001
Volume
281
Issue
4
Pages
866–871
Identifiers
PMID: 11237739
Source
Medline
License
Unknown

Abstract

Apicidin [cyclo(N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-l-2-amino-8-oxodecanoyl)], a novel histone deacetylase inhibitor, has been identified as an antiprotozoal and antiproliferative agent. In this study, we show apicidin induces transcriptional activation of p21(WAF1/CIP1) (p21) in human prostate carcinoma cells. Apicidin induces expression of p21 protein and mRNA and activation of p21 promoter-luciferase reporter constructs. Apicidin causes an accumulation of acetylated histones H3 and H4 in total cellular chromatin. Chromatin immunoprecipitation shows p21 promoter DNA is associated with hyperacetylated histones H3 and H4 after treatment with apicidin. Therefore, the data here demonstrate that apicidin activates p21 transcription associated with the acetylation of histones H3 and H4.

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