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Article: Tumor suppressor p53 as a component of the tumor necrosis factor- induced, protein kinase PKR-mediated apoptotic pathway in human promonocytic U937 cells

TitleTumor suppressor p53 as a component of the tumor necrosis factor- induced, protein kinase PKR-mediated apoptotic pathway in human promonocytic U937 cells
Authors
Issue Date1998
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1998, v. 273 n. 39, p. 25198-25202 How to Cite?
AbstractDespite what is known about the early signaling events in tumor necrosis factor (TNF) α-induced apoptosis, characterization of the downstream events remains largely undefined. It is now known that a crosstalk exists between the interferon and TNF-α pathways. This linkage allows recruitment of the cell proliferation suppressor PKR (dsRNA-dependent protein kinase) from the interferon pathway to play a pivotal role in TNF-α-induced apoptosis. In this study, we took advantage of the differential TNF-α susceptibilities of human promonocytic U937 subclones, deficient in or overexpressing PKR, to further characterize the role of PKR in apoptosis. By reverse transcription- polymerase chain reaction, we demonstrated that TNF-α transiently induces the tumor suppressor p53 in U937 cells. This p53 induction lags behind the TNF-α induction of PKR by 1 h. By cell viability determination, ultrastructural studies, apoptotic DNA laddering, and antisense techniques, it was shown that inhibition of p53 expression in PKR-overexpressing U937 cells abrogates the TNF-α-induced apoptosis in these cells. Conversely, overexpressing wild type p53 in PKR-deficient U937 cells confers the susceptibility of these cells to TNF-α-induced apoptosis. This latter result indicates that p53 induction is an event downstream of TNF-α-induced up- regulation of PKR, thereby further establishing the critical role of p53 in TNF-α-induced apoptosis in U937 cells. PKR-overexpressing U937 cells were found to possess a constitutively higher level of p53, which partly explains why these cells spontaneously undergo apoptosis even without TNF-α treatment. Finally, a model is presented on the interplay between PKR and p53 in effecting TNF-α-induced apoptosis in U937 cells.
Persistent Identifierhttp://hdl.handle.net/10722/170295
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorYeung, MCen_US
dc.contributor.authorLau, ASen_US
dc.date.accessioned2012-10-30T06:07:17Z-
dc.date.available2012-10-30T06:07:17Z-
dc.date.issued1998en_US
dc.identifier.citationJournal Of Biological Chemistry, 1998, v. 273 n. 39, p. 25198-25202en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/170295-
dc.description.abstractDespite what is known about the early signaling events in tumor necrosis factor (TNF) α-induced apoptosis, characterization of the downstream events remains largely undefined. It is now known that a crosstalk exists between the interferon and TNF-α pathways. This linkage allows recruitment of the cell proliferation suppressor PKR (dsRNA-dependent protein kinase) from the interferon pathway to play a pivotal role in TNF-α-induced apoptosis. In this study, we took advantage of the differential TNF-α susceptibilities of human promonocytic U937 subclones, deficient in or overexpressing PKR, to further characterize the role of PKR in apoptosis. By reverse transcription- polymerase chain reaction, we demonstrated that TNF-α transiently induces the tumor suppressor p53 in U937 cells. This p53 induction lags behind the TNF-α induction of PKR by 1 h. By cell viability determination, ultrastructural studies, apoptotic DNA laddering, and antisense techniques, it was shown that inhibition of p53 expression in PKR-overexpressing U937 cells abrogates the TNF-α-induced apoptosis in these cells. Conversely, overexpressing wild type p53 in PKR-deficient U937 cells confers the susceptibility of these cells to TNF-α-induced apoptosis. This latter result indicates that p53 induction is an event downstream of TNF-α-induced up- regulation of PKR, thereby further establishing the critical role of p53 in TNF-α-induced apoptosis in U937 cells. PKR-overexpressing U937 cells were found to possess a constitutively higher level of p53, which partly explains why these cells spontaneously undergo apoptosis even without TNF-α treatment. Finally, a model is presented on the interplay between PKR and p53 in effecting TNF-α-induced apoptosis in U937 cells.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.subject.meshApoptosisen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshCell Lineen_US
dc.subject.meshDna Primersen_US
dc.subject.meshHumansen_US
dc.subject.meshKineticsen_US
dc.subject.meshMicroscopy, Electronen_US
dc.subject.meshNucleosomes - Metabolismen_US
dc.subject.meshTumor Necrosis Factor-Alpha - Metabolismen_US
dc.subject.meshTumor Suppressor Protein P53 - Biosynthesis - Metabolismen_US
dc.subject.meshEif-2 Kinase - Metabolismen_US
dc.titleTumor suppressor p53 as a component of the tumor necrosis factor- induced, protein kinase PKR-mediated apoptotic pathway in human promonocytic 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.doi10.1074/jbc.273.39.25198en_US
dc.identifier.pmid9737981-
dc.identifier.scopuseid_2-s2.0-0032566514en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0032566514&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume273en_US
dc.identifier.issue39en_US
dc.identifier.spage25198en_US
dc.identifier.epage25202en_US
dc.identifier.isiWOS:000076085400031-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridYeung, MC=7101861664en_US
dc.identifier.scopusauthoridLau, AS=7202626202en_US

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