Drug-induced destabilization of bcl-2 mRNA: a new approach for inducing apoptosis in tumor cells.
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.
Otake
Yoko
Y
Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Avenue, PO Box 250509, Charleston, SC 29425, USA.
Sengupta
Tapas K
TK
Bandyopadhyay
Sumita
S
Spicer
Eleanor K
EK
Fernandes
Daniel J
DJ
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism*
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger