Histone deacetylase inhibitors mediate post-transcriptional regulation of p21WAF1 through novel cis-acting elements in the 3' untranslated region.
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.
Department of Biochemistry, University of Saskatchewan, Saskatoon, SK, Canada. clhirsch@mdanderson.org
Calley L
CL
Hirsch
Danielle J P
DJ
Ellis
Keith
K
Bonham
D020413:3' Untranslated Regions / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D020871:RNA Stability; D050436:Regulatory Elements, Transcriptional / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic
D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D056572:Histone Deacetylase Inhibitors