An essential role for the interferon-inducible, double-stranded RNA-activated protein kinase PKR in the tumor necrosis factor-induced apoptosis in U937 cells
In: Proceedings of the National Academy of Sciences, Jg. 93 (1996-10-29), S. 12451-12455
Online
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Zugriff:
Tumor necrosis factor alpha (TNF-alpha) is well-characterized for its necrotic action against tumor cells; however, it has been increasingly associated with an apoptosis-inducing potential on target cells. While the signaling events and the actual cytolytic mechanism(s) for both TNF-alpha-induced necrosis and apoptosis remain to be fully elucidated, we report here on (i) the ability of TNF-alpha to induce apoptosis in the promonocytic U937 cells, (ii) the discovery of a cross-talk between the TNF-alpha and the interferon signaling pathways, and (iii) the pivotal role of interferon-inducible, double-stranded RNA-activated protein kinase (PKR) in the induction of apoptosis by TNF-alpha. Our data from microscopy studies, trypan blue exclusion staining, and apoptotic DNA ladder electrophoresis revealed that a subclone derived from U937 and carrying a PKR antisense expression vector was resistant to TNF-alpha-induced apoptosis. Further, TNF-alpha initiated a generalized RNA degradation process in which the participation of PKR was required. Finally, the PKR gene is a candidate "death gene" since overexpression of this gene could bring about apoptosis in U937 cells.
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An essential role for the interferon-inducible, double-stranded RNA-activated protein kinase PKR in the tumor necrosis factor-induced apoptosis in U937 cells
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Autor/in / Beteiligte Person: | Yeung, Michael C. ; Liu, Jun ; Lau, Allan S. Y. |
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Zeitschrift: | Proceedings of the National Academy of Sciences, Jg. 93 (1996-10-29), S. 12451-12455 |
Veröffentlichung: | Proceedings of the National Academy of Sciences, 1996 |
Medientyp: | unknown |
ISSN: | 1091-6490 (print) ; 0027-8424 (print) |
DOI: | 10.1073/pnas.93.22.12451 |
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