منابع مشابه
Suppression of Bcl-xL deamidation in human hepatocellular carcinomas.
Bcl-xL is an antiapoptotic member of the Bcl-2 family, which inhibits apoptosis initiated by various cellular stresses, and has a pivotal role in the survival of tumor cells. Researchers have previously observed elevated expression of Bcl-xL in some human malignancies. In this study, we present evidence that human Bcl-xL is deamidated at asparagines 52 and 66 and that the rate of Bcl-xL deamida...
متن کاملControl of Cellular Bcl-xL Levels by Deamidation-Regulated Degradation
The cellular concentration of Bcl-xL is among the most important determinants of treatment response and overall prognosis in a broad range of tumors as well as an important determinant of the cellular response to several forms of tissue injury. We and others have previously shown that human Bcl-xL undergoes deamidation at two asparaginyl residues and that DNA-damaging antineoplastic agents as w...
متن کاملInhibition of the Bcl-xL deamidation pathway in myeloproliferative disorders.
BACKGROUND The myeloproliferative disorders are clonal disorders with frequent somatic gain-of-function alterations affecting tyrosine kinases. In these diseases, there is an increase in DNA damage and a risk of progression to acute leukemia. The molecular mechanisms in myeloproliferative disorders that prevent apoptosis induced by damaged DNA are obscure. METHODS We searched for abnormalitie...
متن کاملBcl-xL Deamidation Is a Critical Switch in the Regulation of the Response to DNA Damage
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 aspar...
متن کاملDNA Damage–Induced Bcl-xL Deamidation Is Mediated by NHE-1 Antiport Regulated Intracellular pH
The pro-survival protein Bcl-xL is critical for the resistance of tumour cells to DNA damage. We have previously demonstrated, using a mouse cancer model, that oncogenic tyrosine kinase inhibition of DNA damage-induced Bcl-xL deamidation tightly correlates with T cell transformation in vivo, although the pathway to Bcl-xL deamidation remains unknown and its functional consequences unclear. We s...
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ژورنال
عنوان ژورنال: Molecular Cell
سال: 2002
ISSN: 1097-2765
DOI: 10.1016/s1097-2765(02)00693-7