Human embryonic stem cells have constitutively active Bax at the Golgi and are primed to undergo rapid apoptosis.
Human embryonic stem cells have constitutively active Bax at the Golgi and are primed to undergo rapid apoptosis.
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DOI：
10.1016/j.molcel.2012.04.002
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发表时间：
2012-06-08
期刊：
影响因子：
16
通讯作者：
Deshmukh, Mohanish
中科院分区：
文献类型：
--
作者：
Dumitru, Raluca;Gama, Vivian;Fagan, B. Matthew;Bower, Jacquelyn J.;Swahari, Vijay;Pevny, Larysa H.;Deshmukh, Mohanish
人类胚胎干细胞(HES)在DNA损伤后激活快速的细胞凋亡反应，但其潜在的机制尚不清楚。Bax是细胞凋亡的关键介质，据报道，Bax只有在受到凋亡刺激后才会变得活跃并转移到线粒体。在这里，我们表明，未分化的HES细胞结构性地维持其活性构象中的Bax。令人惊讶的是，活跃的Bax在高尔基体而不是线粒体保持活跃，从而使HES细胞有效地将与预激活Bax相关的风险降至最低。DNA损伤后，Bax活性通过P53依赖的机制迅速转移到线粒体。有趣的是，在分化后，Bax不再活跃，细胞对DNA损伤不再敏感。因此，保持Bax的活性是一种独特的机制，可以为HES细胞的快速死亡做好准备，可能会在胚胎发育的早期关键阶段阻止突变的传播。
Human embryonic stem (hES) cells activate a rapid apoptotic response after DNA damage but the underlying mechanisms are unknown. A critical mediator of apoptosis is Bax, which is reported to become active and translocate to the mitochondria only after apoptotic stimuli. Here we show that undifferentiated hES cells constitutively maintain Bax in its active conformation. Surprisingly, active Bax was maintained at the Golgi rather than at the mitochondria, thus allowing hES cells to effectively minimize the risks associated with having pre-activated Bax. After DNA damage, active Bax rapidly translocated to the mitochondria by a p53-dependent mechanism. Interestingly, upon differentiation, Bax was no longer active and cells were not acutely sensitive to DNA damage. Thus, maintenance of Bax in its active form is a unique mechanism that can prime hES cells for rapid death, likely to prevent the propagation of mutations during the early critical stages of embryonic development.
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影响因子：
1.2
作者：
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发表时间：
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影响因子：
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影响因子：
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影响因子：
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作者：
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