Histone deacetylase inhibitors: signalling towards p21cip1/waf1

Int J Biochem Cell Biol. 2007;39(7-8):1367-74. doi: 10.1016/j.biocel.2007.03.001. Epub 2007 Mar 7.


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.

Publication types

  • Review

MeSH terms

  • Acetylation
  • Apoptosis / physiology
  • Cell Cycle / physiology
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Histone Deacetylase Inhibitors*
  • Histone Deacetylases / metabolism
  • Histones / metabolism
  • Humans
  • Signal Transduction*
  • Tumor Suppressor Protein p53 / metabolism*
  • Up-Regulation*


  • Cyclin-Dependent Kinase Inhibitor p21
  • Histone Deacetylase Inhibitors
  • Histones
  • Tumor Suppressor Protein p53
  • Histone Deacetylases