Histone deacetylase inhibitors regulate p21WAF1 gene expression at the post-transcriptional level in HepG2 cells

FEBS Lett. 2004 Jul 16;570(1-3):37-40. doi: 10.1016/j.febslet.2004.06.018.

Abstract

Histone deacetylase inhibitors (HDIs) are thought to act primarily at the level of transcription inducing cell cycle arrest, differentiation and/or apoptosis in many cancer cell types. Induction of the potent cdk/cyclin inhibitor p21WAF1 is a key feature of this HDI mediated transcriptional re-programming phenomenon. However, in the current study we report that HDIs are also capable of inducing p21WAF1 through purely post-transcriptional events, namely increased mRNA stability. These studies highlight our growing appreciation for the complexities of HDI mediated effects and challenge our preconceptions regarding the action of these promising anti-neoplastics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Blotting, Northern
  • Cell Differentiation
  • Cell Division
  • Cell Line
  • Chloramphenicol O-Acetyltransferase / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression Regulation*
  • Histone Deacetylase Inhibitors*
  • Histones / metabolism
  • Humans
  • Immunoblotting
  • Luciferases / metabolism
  • Plasmids / metabolism
  • Promoter Regions, Genetic
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Time Factors
  • Transcription, Genetic
  • Transcriptional Activation
  • Transfection

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Enzyme Inhibitors
  • Histone Deacetylase Inhibitors
  • Histones
  • RNA, Messenger
  • RNA
  • Luciferases
  • Chloramphenicol O-Acetyltransferase