14-3-3 Proteins are Regulators of Autophagy.
14-3-3 Proteins are Regulators of Autophagy.
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DOI：
10.3390/cells1040754
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发表时间：
2012-10-15
期刊：
影响因子：
6
通讯作者：
Pozuelo-Rubio M
中科院分区：
文献类型：
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作者：
Pozuelo-Rubio M
14-3-3蛋白参与调节多种信号通路中涉及的蛋白。14-3-3-依赖性蛋白调节通过磷酸化依赖性结合发生，在许多情况下，磷酸化依赖性结合导致细胞中存活信号的释放。自噬是一种细胞消化过程，有助于克服营养缺乏，并在应激条件下启动。然而，自噬是细胞存活还是细胞死亡机制仍在讨论中，可能取决于上下文。然而，自噬是决定细胞命运的细胞过程，并且受到不同信号传导途径的严格调节，其中一些信号传导途径，例如MAPK、PI 3 K和mTOR，受到14-3-3蛋白的严格调节。因此，了解14-3-3蛋白在调节自噬过程中的作用是重要的。在这种情况下，14-3-3与mTOR调节蛋白如TSC 2和PRAS 40的直接结合将14-3-3与自噬调节过程连接。此外，14-3-3与人空泡蛋白分选34（hVps 34）（一种III类磷脂酰肌醇-3-激酶（PI 3 KC 3））的结合表明14-3-3蛋白参与调节自噬体形成。hVps 34参与囊泡运输过程如自噬，并且其活化是自噬起始所需的。层析和覆盖技术表明，hVps 34直接与14-3-3蛋白在生理条件下相互作用，从而保持hVps 34在一个非活性状态。相反，营养饥饿促进14-3-3-hVps 34复合物的解离，从而增强hVps 34脂质激酶活性。因此，14-3-3蛋白通过调节自噬机制的关键组分而成为自噬的调节剂。本文综述了14-3-3蛋白在调控自噬主开关的靶蛋白中的作用。
14-3-3 proteins are implicated in the regulation of proteins involved in a variety of signaling pathways. 14-3-3-dependent protein regulation occurs through phosphorylation-dependent binding that results, in many cases, in the release of survival signals in cells. Autophagy is a cell digestion process that contributes to overcoming nutrient deprivation and is initiated under stress conditions. However, whether autophagy is a cell survival or cell death mechanism remains under discussion and may depend on context. Nevertheless, autophagy is a cellular process that determines cell fate and is tightly regulated by different signaling pathways, some of which, for example MAPK, PI3K and mTOR, are tightly regulated by 14-3-3 proteins. It is therefore important to understand the role of 14-3-3 protein in modulating the autophagic process. Within this context, direct binding of 14-3-3 to mTOR regulatory proteins, such as TSC2 and PRAS40, connects 14-3-3 with autophagy regulatory processes. In addition, 14-3-3 binding to human vacuolar protein sorting 34 (hVps34), a class III phosphatidylinositol-3-kinase (PI3KC3), indicates the involvement of 14-3-3 proteins in regulating autophagosome formation. hVps34 is involved in vesicle trafficking processes such as autophagy, and its activation is needed for initiation of autophagy. Chromatography and overlay techniques suggest that hVps34 directly interacts with 14-3-3 proteins under physiological conditions, thereby maintaining hVps34 in an inactive state. In contrast, nutrient starvation promotes dissociation of the 14-3-3–hVps34 complex, thereby enhancing hVps34 lipid kinase activity. Thus, 14-3-3 proteins are regulators of autophagy through regulating key components of the autophagic machinery. This review summarizes the role of 14-3-3 protein in the control of target proteins involved in regulating the master switches of autophagy.