Nix directly binds to GABARAP A possible crosstalk between apoptosis and autophagy
Nix directly binds to GABARAP A possible crosstalk between apoptosis and autophagy
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DOI：
10.4161/auto.5.5.8494
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发表时间：
2009-07-01
期刊：
影响因子：
13.3
通讯作者：
Willbold, Dieter
中科院分区：
文献类型：
--
作者：
Schwarten, Melanie;Mohrlueder, Jeannine;Willbold, Dieter
自噬是一种主要与细胞生存相关的途径，而细胞凋亡是一种总是导致细胞死亡的过程，是细胞自我毁灭的两种主要机制，在细胞生长、神经变性、肿瘤抑制、应激和免疫反应中至关重要。目前，由于最近一些直接连接变得明显，细胞凋亡和自噬之间的潜在串扰正在受到深入研究。然而，各自的蛋白质-蛋白质相互作用网络仍有待详细阐明。 A 型γ-氨基丁酸 (GABA(A)) 受体相关蛋白 GABARAP 属于参与细胞内转运事件的蛋白家族，并被证明与自噬过程相关。通过针对靶蛋白 GABARAP 的噬菌体展示筛选，我们鉴定出促凋亡蛋白 Nix/Bnip3L 是潜在的 GABARAP 配体。体外结合研究、下拉分析、共免疫沉淀分析和共定位研究证实了哺乳动物细胞中两种蛋白质的直接相互作用。
Autophagy, a pathway primarily relevant for cell survival, and apoptosis, a process invariably leading to cell death, are the two main mechanisms of cellular self-destruction, which are essential in cell growth, neurodegeneration, tumor suppression, stress and immune response. Currently, a potential crosstalk between apoptosis and autophagy is subject to intensive investigations since recently some direct junctions became obvious. The respective protein-protein interaction network, however, remains to be elucidated in detail. The gamma-aminobutyric acid type A (GABA(A)) receptor-associated protein GABARAP belongs to a family of proteins implicated in intracellular transport events and was shown to be associated to autophagic processes. Using a phage display screening against the target protein GABARAP, we identified the proapoptotic protein Nix/Bnip3L to be a potential GABARAP ligand. In vitro binding studies, pull-down analysis, coimmunoprecipitation assays and colocalization studies confirmed a direct interaction of both proteins in mammalian cells.