Caspase-3-dependent and -independent degradation of 28 S ribosomal RNA may be involved in the inhibition of protein synthesis during apoptosis initiated by death receptor engagement.
Activation of death receptors initiates intrinsic apoptosis programs in various parts of the cell. To explore the possibility that ribosomal RNA (rRNA), essential for translation in ribosomes, is a target of pro-apoptotic proteins, rRNA was analyzed by electrophoresis in two apoptosis systems: human Jurkat cells treated with anti-Fas antibody and human U937 cells treated with tumor necrosis factor-alpha. In both systems, bands in addition to those of unmodified rRNA were detected a few hours after death receptor engagement. In both systems, the primary additional band was identical and comprised the 3'-terminal region of 28 S rRNA. The degradation of 28 S rRNA was simultaneous with protein synthesis inhibition in both systems. The caspase-3 inhibitor Z-DEVD-FMK suppressed rRNA degradation and protein synthesis inhibition in Jurkat cells but not in U937 cells. Together, our data suggest that different pathways are activated in the two systems we studied, and the final steps in these pathways use very similar or identical ribonucleases to cleave 28 S rRNA. These data suggest a physiological link between rRNA degradation and inhibition of protein synthesis. In general, apoptosis execution initiated by death receptor engagement is promoted by protein synthesis inhibition. Triggered by rRNA degradation, malfunction of the protein synthesis machinery may prompt death execution.
Nadano
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Molecular Oncology Laboratory, Tsukuba Life Science Center, RIKEN (Institute of Physical and Chemical Research), Tsukuba, Ibaraki 305-0074, Japan.
Sato
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TA
D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D014176:Protein Biosynthesis; D012339:RNA, Ribosomal, 28S / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D020298:U937 Cells
D012339:RNA, Ribosomal, 28S; D011956:Receptors, Cell Surface; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases