Protein synthesis persists during necrotic cell death.
Cell death is an intrinsic part of metazoan development and mammalian immune regulation. Whereas the molecular events orchestrating apoptosis have been characterized extensively, little is known about the biochemistry of necrotic cell death. Here, we show that, in contrast to apoptosis, the induction of necrosis does not lead to the shut down of protein synthesis. The rapid drop in protein synthesis observed in apoptosis correlates with caspase-dependent breakdown of eukaryotic translation initiation factor (eIF) 4G, activation of the double-stranded RNA-activated protein kinase PKR, and phosphorylation of its substrate eIF2-alpha. In necrosis induced by tumor necrosis factor, double-stranded RNA, or viral infection, de novo protein synthesis persists and 28S ribosomal RNA fragmentation, eIF2-alpha phosphorylation, and proteolytic activation of PKR are absent. Collectively, these results show that, in contrast to apoptotic cells, necrotic dying cells retain the opportunity to synthesize proteins.
Saelens
Xavier
X
Molecular Signalling and Cell Death Unit, Department for Molecular Biomedical Research, Flanders Interuniversity Institute for Biotechnology (VIB) and Ghent University, B9052 Ghent, Belgium.
Festjens
Nele
N
Parthoens
Eef
E
Vanoverberghe
Isabel
I
Kalai
Michael
M
van Kuppeveld
Frank
F
Vandenabeele
Peter
P
D017209:Apoptosis / Q000502:physiology*; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D004770:Enterovirus / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism*; D019254:Genes, bcl-2 / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells; D009336:Necrosis / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000502:physiology; D012339:RNA, Ribosomal, 28S / Q000378:metabolism*; D012270:Ribosomes / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured; D048069:Tumor Necrosis Factors / Q000502:physiology; D019892:eIF-2 Kinase / Q000378:metabolism*
D015852:Eukaryotic Initiation Factor-2; D012330:RNA, Double-Stranded; D012339:RNA, Ribosomal, 28S; D048069:Tumor Necrosis Factors; D019892:eIF-2 Kinase; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases