Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
Autophagy. 2012 Mar;8(3):433-4. doi: 10.4161/auto.19288. Epub 2012 Feb 3.
Reactive oxygen species (ROS) that accumulate under oxidative pressure cause severe damage to cellular components, and induce various cellular responses, including apoptosis, programmed necrosis and autophagy, depending on the cellular setting. Various studies have described ROS-induced autophagy, but only a few direct factors that regulate autophagy under oxidative stress are known to date. We have identified DAPK and PKD as such regulators by demonstrating their role in the process of autophagy in general, and specifically during oxidative stress. PKD acts as a downstream effector of DAPk in the regulation of autophagy. Furthermore, PKD functions within the autophagic network as an activator of VPS34, by associating with and phosphorylating VPS34, leading to its activation. Significantly, PKD is recruited to the autophagosomal membranes, placing it within proximity of its autophagic target.
活性氧（ROS）在氧化压力下积累会对细胞成分造成严重损害，并根据细胞环境诱导各种细胞反应，包括细胞凋亡、程序性坏死和自噬。已有研究描述了 ROS 诱导的自噬，但迄今为止，只有少数已知的直接调节氧化应激下自噬的因素。我们通过证明 DAPK 和 PKD 在自噬过程中的作用，特别是在氧化应激下的作用，确定了它们是这样的调节因子。PKD 作为 DAPK 在自噬调节中的下游效应物发挥作用。此外，PKD 作为 VPS34 的激活剂，通过与 VPS34 结合并磷酸化 VPS34，在自噬网络中发挥作用，从而导致其激活。重要的是，PKD 被招募到自噬体膜上，使其接近自噬的靶标。
