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