A critical role of eEF-2K in mediating autophagy in response to multiple cellular stresses.

A critical role of eEF-2K in mediating autophagy in response to multiple cellular stresses.
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DOI:
10.4161/auto.5.3.7762
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发表时间:
2009-04
期刊:
影响因子:
13.3
通讯作者:
Yuan J
Yuan J
中科院分区:
生物学1区
文献类型:
--
作者:
Py BF;Boyce M;Yuan J

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真核生物翻译起始因子2 (eIF2α)亚基α的磷酸化是控制蛋白质翻译的关键调控事件,最近被发现介导自噬的诱导。然而,eIF2α下游的自噬介质尚不清楚。在这里,我们提供的证据表明,eIF2α磷酸化是营养饥饿期间真核延伸因子2 (eEF-2)磷酸化所必需的。此外,我们发现真核延伸因子2激酶(eEF-2K)也是内质网胁迫下自噬信号传递所必需的,这表明eEF-2的磷酸化可能是自噬信号传递的各种细胞胁迫的整合者。另一方面,尽管eEF-2K在饥饿反应中的激活需要eIF2α的磷酸化,但在内质网应激中,部分依赖于Ca2+通量的其他途径可能控制eEF-2K的活性,因为在这种情况下,eIF2α的磷酸化对于eEF-2的磷酸化和自噬都是必不可少的。
The phosphorylation of the subunit α of eukaryotic translation initiation factor 2 (eIF2α), a critical regulatory event in controlling protein translation, has recently been found to mediate the induction of autophagy. However, the mediators of autophagy downstream of eIF2α remain unknown. Here, we provide evidence that eIF2α phosphorylation is required for phosphorylation of eukaryotic elongation factor 2 (eEF-2) during nutrient starvation. In addition, we show that eukaryotic elongation factor 2 kinase (eEF-2K) is also required for autophagy signaling during ER stress, suggesting that phosphorylation of eEF-2 may serve as an integrator of various cell stresses for autophagy signaling. On the other hand, although the activation of eEF-2K in response to starvation requires the phosphorylation of eIF2α, additional pathways relying partly on Ca2+ flux may control eEF-2K activity during ER stress, as eIF2α phosphorylation is dispensable for both eEF-2 phosphorylation and autophagy in this context.
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