PKD at the crossroads of necrosis and autophagy.
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.
Department of Molecular Genetics, The Weizmann Institute of Science, Rehovot, Israel.
Avital
A
Eisenberg-Lerner
Adi
A
Kimchi
D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002460:Cell Line; D064550:Death-Associated Protein Kinases; D059865:Endoplasmic Reticulum Stress; D006801:Humans; D009336:Necrosis; D018384:Oxidative Stress; D010588:Phagosomes / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D051017:Apoptosis Regulatory Proteins; D017382:Reactive Oxygen Species; C089212:protein kinase D; D064550:Death-Associated Protein Kinases; D011493:Protein Kinase C; D017871:Calcium-Calmodulin-Dependent Protein Kinases