Differential dependence on Beclin 1 for the regulation of pro-survival autophagy by Bcl-2 and Bcl-xL in HCT116 colorectal cancer cells.
Differential dependence on Beclin 1 for the regulation of pro-survival autophagy by Bcl-2 and Bcl-xL in HCT116 colorectal cancer cells.
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DOI：
10.1371/journal.pone.0008755
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发表时间：
2010-01-18
期刊：
影响因子：
3.7
通讯作者：
Vallette FM
中科院分区：
文献类型：
--
作者：
Priault M;Hue E;Marhuenda F;Pilet P;Oliver L;Vallette FM
自噬被描述为参与体内平衡、发育和疾病，作为生存和死亡过程。它参与细胞死亡是由于与细胞凋亡途径的相互关系。我们专注于生存自噬并研究其与细胞凋亡机制的相互作用。我们发现，虽然 Mcl-1 仍然无效，但饥饿细胞需要 Bcl-2 和 Bcl-xL 才能显示出功能齐全的自噬途径，如蛋白水解活性和自噬囊泡检测所示。 Bcl-2 和 Bcl-xL 的这种促自噬功能独立于 Bax。然而，它们似乎通过非冗余机制进行操作，因为 Bcl-xL 对自噬的调节比 Bcl-2 具有更严格的控制：与 Bcl-2 不同，Bcl-xL 和 Atg7 操作产生相同的表型，表明它们可能是同一信号通路的组成部分； Bcl-xL 亚细胞定位在饥饿时发生改变，重要的是，Bcl-xL 的作用独立于 Beclin 1。Bcl-xL 仍然需要完整的 BH3 结合位点才能刺激功能齐全的自噬途径。这项研究强调，除了在细胞凋亡过程中具有完善的抗死亡功能外，Bcl-2 和 Bcl-xL 在细胞存活中发挥着更广泛的作用。如果Bcl-2和Bcl-xL处于促生存和促死亡自噬的十字路口，本研究引入了新概念，即Bcl-2和Bcl-xL对自噬的调节根据其生存或死亡结果进行调整。
Autophagy is described to be involved in homeostasis, development and disease, both as a survival and a death process. Its involvement in cell death proceeds from interrelationships with the apoptotic pathway. We focused on survival autophagy and investigated its interplays with the apoptotic machinery. We found that while Mcl-1 remained ineffective, Bcl-2 and Bcl-xL were required for starved cells to display a fully functional autophagic pathway as shown by proteolysis activity and detection of autophagic vesicles. Such pro-autophagic functions of Bcl-2 and Bcl-xL were independent of Bax. However they appeared to operate through non redundant mechanisms as Bcl-xL wielded a tighter control than Bcl-2 over the regulation of autophagy: unlike Bcl-2, Bcl-xL and Atg7 manipulation yielded identical phenotypes suggesting they could be components of the same signalling pathway; Bcl-xL subcellular localisation was modified upon starvation, and importantly Bcl-xL acted independently of Beclin 1. Still an intact BH3-binding site was required for Bcl-xL to stimulate a fully functional autophagic pathway. This study highlights that, in addition to their well-established anti-death function during apoptosis, Bcl-2 and Bcl-xL have a broader role in cell survival. Should Bcl-2 and Bcl-xL stand at the cross-roads between pro-survival and pro-death autophagy, this study introduces the new concept that the regulation of autophagy by Bcl-2 and Bcl-xL is adjusted according to its survival or death outcome.
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影响因子：
3.2
作者：
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