Endoplasmic reticulum stress initiates apoptotic death induced by STI571 inhibition of p210 bcr-abl tyrosine kinase

被引：24

作者：

Pattacini, L ^{[1
]}

Mancini, M ^{[1
]}

Mazzacurati, L ^{[1
]}

Brusa, G ^{[1
]}

Benvenuti, M ^{[1
]}

Martinelli, G ^{[1
]}

Baccarani, M ^{[1
]}

Santucci, MA ^{[1
]}

机构：

[1] Univ Bologna, Sch Med, S Orsola Hosp, Ist Ematol & Oncol Med Lorenzo & Ariosto Seragnol, I-40138 Bologna, Italy

来源：

LEUKEMIA RESEARCH | 2004年 / 28卷 / 02期

关键词：

Chronic Myeloid Leukemia; STI571; apoptosis; ER stress; Bad; Bcl-2; caspase; 12;

D O I：

10.1016/S0145-2126(03)00218-2

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

The endoplasmic reticulum (ER) is the site where proteins. destined to either secretion or different subcellular compartments assemble and the major storage of intracellular Ca2+. The ER stress resulting from a variety of toxic insults leads to apoptosis. Here, we showed that the apoptotic death triggered by ST1571, an inhibitor of the p210 bcr-abl tyrosine kinase, in murine myeloid progenitors transducing the p210 bcr-abl! tyrosine kinase of Chronic Myeloid Leukemia (CML) proceeds from ER stress. The Bcl-2 dowmodulation and inactivation induced by the binding to its antagonist: Bad, the release of caspase 12 from the ER membranes in its active form and of Ca2+ from the ER pool addressed towards ER a sensor of ST1571-induced pro-apoptotic signal. (C) 2003 Elsevier Ltd. All rights reserved.

引用

页码：191 / 202

页数：12

共 46 条

[1] Bcl-2-independent Bcr-Abl-mediated resistance to apoptosis:: protection is correlated with up regulation of Bcl-xL [J].