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Curr Opin Investig Drugs. 2004 Jun;5(6):616-22.

Drug-induced destabilization of bcl-2 mRNA: a new approach for inducing apoptosis in tumor cells.

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1
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, PO Box 250509, Charleston, SC 29425, USA.

Abstract

Recent evidence suggests that the 3' untranslated region (3' UTR) of some mRNAs is a molecular hotspot for pathology. The 3' UTR of bcl-2 mRNA contains several AU-rich elements (AREs) that promote mRNA destabilization. Recent studies have demonstrated that the protein, nucleolin, binds to an ARE in bcl-2 mRNA, thereby protecting this mRNA from nuclease degradation. All-trans retinoic acid, taxol and okadiac acid induce downregulation or inactivation of nucleolin, which destabilizes bcl-2 mRNA and triggers apoptosis. The ARE instability elements in bcl-2 mRNA are potential therapeutic targets for inducing apoptosis and overcoming drug resistance in cancer cells.

PMID:
15242250
[Indexed for MEDLINE]
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