Abstract:
: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.
journal_name
Celljournal_title
Cellauthors
Deverman BE,Cook BL,Manson SR,Niederhoff RA,Langer EM,Rosová I,Kulans LA,Fu X,Weinberg JS,Heinecke JW,Roth KA,Weintraub SJdoi
10.1016/s0092-8674(02)00972-8subject
Has Abstractpub_date
2002-10-04 00:00:00pages
51-62issue
1eissn
0092-8674issn
1097-4172pii
S0092867402009728journal_volume
111pub_type
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