药物诱导的bcl-2 mRNA不稳定：诱导肿瘤细胞凋亡的新方法。

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

作者信息

Otake Yoko, Sengupta Tapas K, Bandyopadhyay Sumita, Spicer Eleanor K, Fernandes Daniel J

机构信息

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

出版信息

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

PMID:15242250

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.

摘要

最近的证据表明，某些mRNA的3'非翻译区（3'UTR）是病理学的分子热点。bcl-2 mRNA的3'UTR包含几个富含AU的元件（ARE），这些元件可促进mRNA的不稳定。最近的研究表明，核仁素蛋白与bcl-2 mRNA中的一个ARE结合，从而保护该mRNA不被核酸酶降解。全反式维甲酸、紫杉醇和冈田酸可诱导核仁素的下调或失活，从而使bcl-2 mRNA不稳定并触发细胞凋亡。bcl-2 mRNA中的ARE不稳定元件是诱导癌细胞凋亡和克服耐药性的潜在治疗靶点。