Beclin 1 Phosphorylation - at the Center of Autophagy Regulation.
Beclin 1 Phosphorylation - at the Center of Autophagy Regulation.
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DOI：
10.3389/fcell.2018.00137
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发表时间：
2018
影响因子：
5.5
通讯作者：
Dhamija S
中科院分区：
文献类型：
--
作者：
Menon MB;Dhamija S
自噬是一种受到严格调节的分解代谢过程，其中处于压力下的细胞将胞浆成分（例如受损的蛋白质和细胞器）隔离在称为自噬体的双膜囊泡中。自噬体通过溶酶体蛋白水解降解其货物，产生用于生物合成重要大分子的原料。自噬体从自噬前结构组装的初始步骤之一是募集和激活由Beclin 1（BECN 1）、VPS 34、VPS 15和ATG 14蛋白组成的III类磷脂酰肌醇3-激酶复合物。一些证据表明，BECN 1在一系列残基上的磷酸化和泛素化微调了对不同自噬调节刺激的反应，并有助于维持促生存自噬和促凋亡反应之间的平衡。在这篇简短的综述中，我们将讨论不同的BECN 1磷酸化事件的重要性，所涉及的不同信号通路和激酶及其在自噬调控中的作用。
Autophagy is a tightly regulated catabolic process wherein cells under stress sequester cytosolic constituents like damaged proteins and organelles in double-membrane vesicles called autophagosomes. The autophagosomes degrade their cargo by lysosomal proteolysis generating raw materials for the biosynthesis of vital macromolecules. One of the initial steps in the assembly of autophagosomes from pre-autophagic structures is the recruitment and activation of the class III phosphatidylinositol 3-kinase complex consisting of Beclin 1 (BECN1), VPS34, VPS15, and ATG14 proteins. Several pieces of evidence indicate that the phosphorylation and ubiquitination of BECN1 at an array of residues fine-tune the responses to diverse autophagy modulating stimuli and helps in maintaining the balance between pro-survival autophagy and pro-apoptotic responses. In this mini-review, we will discuss the importance of distinct BECN1 phosphorylation events, the diverse signaling pathways and kinases involved and their role in the regulation of autophagy.