Endoplasmic reticulum stress signaling transmitted by ATF6 mediates apoptosis during muscle development.
Endoplasmic reticulum stress signaling transmitted by ATF6 mediates apoptosis during muscle development.
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DOI：
10.1083/jcb.200412024
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发表时间：
2005-05-23
影响因子：
7.8
通讯作者：
Morishima, Nobuhiro
中科院分区：
文献类型：
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作者：
Nakanishi, Keiko;Sudo, Tatsuhiko;Morishima, Nobuhiro
虽然细胞凋亡发生在肌细胞发生过程中，但其启动机制尚不清楚。在一个培养模型中，我们展示了caspase-12的激活，它是内质网(ER)应激特异性caspase级联的启动者，在与成肌细胞分化相关的凋亡过程中。在凋亡和分化细胞中也观察到内质网应激反应蛋白(Bip和CHOP)的诱导。ATF6，而不是其他内质网应激感受器，在成肌细胞的凋亡过程中被特异性地激活，这表明部分但选择性地激活内质网应激信号足以诱导细胞凋亡。在小鼠胚胎的发育肌肉中也检测到caspase-12的激活，并在以后逐渐消失。CHOP也是一过性的。这些结果表明，ATF6传递的特定内质网应激信号导致肌肉发育过程中自然发生的细胞凋亡。
Although apoptosis occurs during myogenesis, its mechanism of initiation remains unknown. In a culture model, we demonstrate activation of caspase-12, the initiator of the endoplasmic reticulum (ER) stress-specific caspase cascade, during apoptosis associated with myoblast differentiation. Induction of ER stress-responsive proteins (BiP and CHOP) was also observed in both apoptotic and differentiating cells. ATF6, but not other ER stress sensors, was specifically activated during apoptosis in myoblasts, suggesting that partial but selective activation of ER stress signaling was sufficient for induction of apoptosis. Activation of caspase-12 was also detected in developing muscle of mouse embryos and gradually disappeared later. CHOP was also transiently induced. These results suggest that specific ER stress signaling transmitted by ATF6 leads to naturally occurring apoptosis during muscle development.