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

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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 p21WAF1. However, HDACIs primarily increase p21WAF1 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 p21WAF1 are identified that control the ability of HDACIs to induce p21WAF1 mRNA stabilization. Collectively, these studies highlight the complexity of HDACIs in gene regulation.