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Article: An essential role for the interferon-inducible, double-stranded RNA-activated protein kinase PKR in the tumor necrosis factor-induced apoptosis in U937 cells

TitleAn essential role for the interferon-inducible, double-stranded RNA-activated protein kinase PKR in the tumor necrosis factor-induced apoptosis in U937 cells
Authors
Issue Date1996
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings Of The National Academy Of Sciences Of The United States Of America, 1996, v. 93 n. 22, p. 12451-12455 How to Cite?
AbstractTumor necrosis factor α (TNF-α) 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-α-induced necrosis and apoptosis remain to be fully elucidated, we report here on (i) the ability of TNF-α to induce apoptosis in the promonocytic U937 cells, (ii) the discovery of a cross-talk between the TNF-α 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-α. 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-α-induced apoptosis. Further, TNF-α 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.
Persistent Identifierhttp://hdl.handle.net/10722/170281
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYeung, MCen_US
dc.contributor.authorLiu, Jen_US
dc.contributor.authorLau, ASen_US
dc.date.accessioned2012-10-30T06:07:12Z-
dc.date.available2012-10-30T06:07:12Z-
dc.date.issued1996en_US
dc.identifier.citationProceedings Of The National Academy Of Sciences Of The United States Of America, 1996, v. 93 n. 22, p. 12451-12455en_US
dc.identifier.issn0027-8424en_US
dc.identifier.urihttp://hdl.handle.net/10722/170281-
dc.description.abstractTumor necrosis factor α (TNF-α) 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-α-induced necrosis and apoptosis remain to be fully elucidated, we report here on (i) the ability of TNF-α to induce apoptosis in the promonocytic U937 cells, (ii) the discovery of a cross-talk between the TNF-α 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-α. 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-α-induced apoptosis. Further, TNF-α 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.en_US
dc.languageengen_US
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.orgen_US
dc.relation.ispartofProceedings of the National Academy of Sciences of the United States of Americaen_US
dc.subject.meshApoptosis - Drug Effectsen_US
dc.subject.meshCell Survival - Drug Effectsen_US
dc.subject.meshEnzyme Inductionen_US
dc.subject.meshHumansen_US
dc.subject.meshInterferons - Pharmacologyen_US
dc.subject.meshLeukemia, Myeloid - Metabolism - Pathologyen_US
dc.subject.meshProtein-Serine-Threonine Kinases - Metabolismen_US
dc.subject.meshRna, Ribosomal, 18S - Metabolismen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.subject.meshTumor Necrosis Factor-Alpha - Pharmacologyen_US
dc.subject.meshUp-Regulation - Drug Effectsen_US
dc.subject.meshEif-2 Kinaseen_US
dc.titleAn essential role for the interferon-inducible, double-stranded RNA-activated protein kinase PKR in the tumor necrosis factor-induced apoptosis in U937 cellsen_US
dc.typeArticleen_US
dc.identifier.emailLau, AS:asylau@hku.hken_US
dc.identifier.authorityLau, AS=rp00474en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1073/pnas.93.22.12451-
dc.identifier.pmid8901602-
dc.identifier.scopuseid_2-s2.0-0029981093en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0029981093&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume93en_US
dc.identifier.issue22en_US
dc.identifier.spage12451en_US
dc.identifier.epage12455en_US
dc.identifier.isiWOS:A1996VP93700073-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYeung, MC=7101861664en_US
dc.identifier.scopusauthoridLiu, J=36071959600en_US
dc.identifier.scopusauthoridLau, AS=7202626202en_US

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