SOK1 translocates from the Golgi to the nucleus upon chemical anoxia and induces apoptotic cell death.
SOK1 is a Ste20 protein kinase of the germinal center kinase (GCK) family that has been shown to be activated by oxidant stress and chemical anoxia, a cell culture model of ischemia. More recently, it has been shown to be localized to the Golgi apparatus, where it functions in a signaling pathway required for cell migration and polarization. Herein, we demonstrate that SOK1 regulates cell death after chemical anoxia, as its down-regulation by RNA interference enhances cell survival. Furthermore, expression of SOK1 elicits apoptotic cell death by activating the intrinsic pathway. We also find that a cleaved form of SOK1 translocates from the Golgi to the nucleus after chemical anoxia and that this translocation is dependent on both caspase activity and on amino acids 275-292, located immediately C-terminal to the SOK1 kinase domain. Furthermore, SOK1 entry into the nucleus is important for the cell death response since SOK1 mutants unable to enter the nucleus do not induce cell death. In summary, SOK1 is necessary to induce cell death and can induce death when overexpressed. Furthermore, SOK1 appears to play distinctly different roles in stressed versus non-stressed cells, regulating cell death in the former.
Nogueira
Emilio
E
Department of Physiology, School of Medicine, University of Santiago de Compostela, 15705 Santiago de Compostela, Spain.
Fidalgo
Miguel
M
Molnar
Arpad
A
Kyriakis
John
J
Force
Thomas
T
Zalvide
Juan
J
Pombo
Celia M
CM
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D019556:COS Cells; D020169:Caspases / Q000502:physiology; D015687:Cell Hypoxia / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002522:Chlorocebus aethiops; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007511:Ischemia / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D000099317:Hippo Kinases
D020169:Caspases; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C530660:STK25 protein, human; D000099317:Hippo Kinases