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Int J Biochem Cell Biol. 2007;39(7-8):1367-74. Epub 2007 Mar 7.

Histone deacetylase inhibitors: signalling towards p21cip1/waf1.

Author information

1
Department of Medicine 1, University Hospital Erlangen, Erlangen, Germany. Matthias.ocker@med1.imed.uni-erlangen.de

Abstract

Chromatin-modifying enzymes such as histone deacetylases (HDAC) facilitate a closed chromatin structure and hence transcriptional repression. HDAC are commonly affected in human cancer diseases. Thus, inhibition of HDAC represents a novel therapeutic approach. Several studies have shown that HDAC inhibitors strongly activate the expression of the cyclin-dependent kinase inhibitor p21(cip1/waf1) through (i) enhanced histone acetylation around the p21(cip1/waf1) promoter and (ii) the Sp1 sites on the p21(cip1/waf1) promoter releasing the repressor HDAC1 from its binding. p21(cip1/waf1) expression is regulated in a p53-dependent and p53-independent manner. The decision if p21(cip1/waf1) up-regulation results in cell cycle arrest or apoptosis, decides about the therapeutic efficacy of an anti-cancer treatment with HDAC inhibitors.

PMID:
17412634
DOI:
10.1016/j.biocel.2007.03.001
[Indexed for MEDLINE]

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