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Cell. 2002 Oct 4;111(1):51-62.

Bcl-xL deamidation is a critical switch in the regulation of the response to DNA damage.

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Division of Urology, Department of Cell Biology and Physiology, School of Medicine, Washington University, 660 South Euclid Avenue, Campus Box 8052, Saint Louis, MO 63110, USA.

Erratum in

  • Cell. 2003 Nov 14;115(4):503.


The therapeutic value of DNA-damaging antineoplastic agents is dependent upon their ability to induce tumor cell apoptosis while sparing most normal tissues. Here, we show that a component of the apoptotic response to these agents in several different types of tumor cells is the deamidation of two asparagines in the unstructured loop of Bcl-xL, and we demonstrate that deamidation of these asparagines imports susceptibility to apoptosis by disrupting the ability of Bcl-xL to block the proapoptotic activity of BH3 domain-only proteins. Conversely, Bcl-xL deamidation is actively suppressed in fibroblasts, and suppression of deamidation is an essential component of their resistance to DNA damage-induced apoptosis. Our results suggest that the regulation of Bcl-xL deamidation has a critical role in the tumor-specific activity of DNA-damaging antineoplastic agents.

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