Exposure of vital cells to necrotic cell lysates induce the IRE1α branch of the unfolded protein response and cell proliferation |
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| Authors: | Philipp Rohne Steven Wolf Carolin Dörr Julia Ringen Andrew Holtz René Gollan Benjamin Renner Hans Prochnow Markus Baiersdörfer Claudia Koch-Brandt |
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| Institution: | 1.Institute of Pharmacy and Biochemistry - Therapeutical Life Sciences,Johannes Gutenberg University of Mainz,Mainz,Germany;2.Department of Pathology,The University of Chicago,Chicago,USA;3.Department of Neurology, University Medical Center Mainz,Johannes Gutenberg University Mainz,Mainz,Germany;4.Department of Chemical Biology,Helmholtz Centre for Infection Research GmbH,Braunschweig,Germany |
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| Abstract: | Necrosis is a form of cell death that is detrimental to the affected tissue because the cell ruptures and releases its content (reactive oxygen species among others) into the extracellular space. Clusterin (CLU), a cytoprotective extracellular chaperone has been shown to be upregulated in the face of necrosis. We here show that in addition to CLU upregulation, necrotic cell lysates induce JNK/SAPK signaling, the IRE1α branch of the unfolded protein response (UPR), the MAPK/ERK1/2, and the mTOR signaling pathways and results in an enhanced proliferation of the vital surrounding cells. We name this novel response mechanism: Necrosis-induced Proliferation (NiP). |
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