HUNK 通过磷酸化 Rubicon 来支持自噬。
HUNK Phosphorylates Rubicon to Support Autophagy.
机构信息
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC 29425, USA.
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Simon Cancer Center, Indianapolis, IN 46202, USA.
出版信息
Int J Mol Sci. 2019 Nov 19;20(22):5813. doi: 10.3390/ijms20225813.
BACKGROUND
Autophagy is a catabolic cellular recycling pathway that is essential for maintaining intracellular homeostasis. Autophagosome formation is achieved via the coordination of the Beclin-1 protein complex. Rubicon is a Beclin-1 associated protein that suppresses autophagy by impairing the activity of the class III PI3K, Vps34. However, very little is known about the molecular mechanisms that regulate Rubicon function.
METHODS
In this study, co-immunoprecipitation and kinase assays were used to investigate the ability of Hormonally Upregulated Neu-associated Kinase (HUNK) to bind to and phosphorylate Rubicon. LC3B was monitored by immunofluorescence and immunoblotting to determine whether phosphorylation of Rubicon by HUNK controls the autophagy suppressive function of Rubicon.
RESULTS
Findings from this study identify Rubicon as a novel substrate of HUNK and show that phosphorylation of Rubicon inhibits its function, promoting autophagy.
背景
自噬是一种分解代谢的细胞回收途径，对于维持细胞内的稳态至关重要。自噬体的形成是通过 Beclin-1 蛋白复合物的协调来实现的。Rubicon 是一种与 Beclin-1 相关的蛋白，通过损害 class III PI3K（Vps34）的活性来抑制自噬。然而，关于调节 Rubicon 功能的分子机制知之甚少。
方法
在这项研究中，通过免疫共沉淀和激酶测定来研究激素上调神经相关激酶（HUNK）与 Rubicon 结合和磷酸化的能力。通过免疫荧光和免疫印迹来监测 LC3B，以确定 HUNK 对 Rubicon 的磷酸化是否控制 Rubicon 的自噬抑制功能。
结果
本研究确定 Rubicon 是 HUNK 的一个新底物，并表明 Rubicon 的磷酸化抑制其功能，从而促进自噬。
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