Histone deacetylase inhibitors mediate post-transcriptional regulation of p21WAF1 through novel cis-acting elements in the 3' untranslated region

Biochem Biophys Res Commun. 2010 Nov 26;402(4):687-92. doi: 10.1016/j.bbrc.2010.10.085. Epub 2010 Oct 25.

Abstract

Histone deacetylase inhibitors (HDACIs) are promising anti-tumor agents that selectively induce cell cycle arrest, differentiation and/or apoptosis of tumor cells. Fundamentally, HDACIs are proposed to function by activating the transcription of genes, including the potent cyclin dependent kinase inhibitor p21(WAF1). However, HDACIs primarily increase p21(WAF1) expression at the post-transcriptional level in HepG2 cells, implying that these anti-tumor agents regulate genes at multiple levels. Here, two novel cis-acting elements in the 3' untranslated region (UTR) of p21(WAF1) are identified that control the ability of HDACIs to induce p21(WAF1) mRNA stabilization. Collectively, these studies highlight the complexity of HDACIs in gene regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / drug effects*
  • 3' Untranslated Regions / genetics
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Base Sequence
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Gene Expression Regulation / drug effects*
  • Histone Deacetylase Inhibitors / pharmacology*
  • Humans
  • Mice
  • Molecular Sequence Data
  • RNA Stability
  • Regulatory Elements, Transcriptional / drug effects*
  • Regulatory Elements, Transcriptional / genetics
  • Transcription, Genetic

Substances

  • 3' Untranslated Regions
  • Antineoplastic Agents
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Histone Deacetylase Inhibitors