Please use this identifier to cite or link to this item:
http://doi.org/10.25358/openscience-7880
Full metadata record
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Müller, Sylvia | - |
dc.contributor.author | Chen, Yuan | - |
dc.contributor.author | Ginter, Torsten | - |
dc.contributor.author | Schäfer, Claudia | - |
dc.contributor.author | Buchwald, Marc | - |
dc.contributor.author | Schmitz, Lienhard M. | - |
dc.contributor.author | Klitzsch, Jana | - |
dc.contributor.author | Schütz, Alexander | - |
dc.contributor.author | Haitel, Andrea | - |
dc.contributor.author | Schmid, Katharina | - |
dc.contributor.author | Moriggl, Richard | - |
dc.contributor.author | Kenner, Lukas | - |
dc.contributor.author | Friedrich, Karlheinz | - |
dc.contributor.author | Haan, Claude | - |
dc.contributor.author | Petersen, Iver | - |
dc.contributor.author | Heinzel, Thorsten | - |
dc.contributor.author | Krämer, Oliver | - |
dc.date.accessioned | 2022-10-06T07:40:57Z | - |
dc.date.available | 2022-10-06T07:40:57Z | - |
dc.date.issued | 2014 | - |
dc.identifier.uri | https://openscience.ub.uni-mainz.de/handle/20.500.12030/7895 | - |
dc.description.abstract | The Janus tyrosine kinases JAK1-3 and tyrosine kinase-2 (TYK2) are frequently hyperactivated in tumors. In lung cancers JAK1 and JAK2 induce oncogenic signaling through STAT3. A putative role of TYK2 in these tumors has not been reported. Here, we show a previously not recognized TYK2-STAT3 signaling node in lung cancer cells. We reveal that the E3 ubiquitin ligase seven-in-absentia-2 (SIAH2) accelerates the proteasomal degradation of TYK2. This mechanism consequently suppresses the activation of STAT3. In agreement with these data the analysis of primary non-small-cell lung cancer (NSCLC) samples from three patient cohorts revealed that compared to lung adenocarcinoma (ADC), lung squamous cell carcinoma (SCC) show significantly higher levels of SIAH2 and reduced STAT3 phosphorylation levels. Thus, SIAH2 is a novel molecular marker for SCC. We further demonstrate that an activation of the oncologically relevant transcription factor p53 in lung cancer cells induces SIAH2, depletes TYK2, and abrogates the tyrosine phosphorylation of STAT1 and STAT3. This mechanism appears to be different from the inhibition of phosphorylated JAKs through the suppressor of cytokine signaling (SOCS) proteins. Our study may help to identify molecular mechanisms affecting lung carcinogenesis and potential therapeutic targets. | en_GB |
dc.description.sponsorship | DFG, Open Access-Publizieren Universität Mainz / Universitätsmedizin | de |
dc.language.iso | eng | de |
dc.rights | CC BY | * |
dc.rights.uri | https://creativecommons.org/licenses/by/3.0/ | * |
dc.subject.ddc | 610 Medizin | de_DE |
dc.subject.ddc | 610 Medical sciences | en_GB |
dc.title | SIAH2 antagonizes TYK2-STAT3 signaling in lung carcinoma cells | en_GB |
dc.type | Zeitschriftenaufsatz | de |
dc.identifier.doi | http://doi.org/10.25358/openscience-7880 | - |
jgu.type.dinitype | article | en_GB |
jgu.type.version | Published version | de |
jgu.type.resource | Text | de |
jgu.organisation.department | FB 04 Medizin | de |
jgu.organisation.number | 2700 | - |
jgu.organisation.name | Johannes Gutenberg-Universität Mainz | - |
jgu.rights.accessrights | openAccess | - |
jgu.journal.title | OncoTarget | de |
jgu.journal.volume | 5 | de |
jgu.journal.issue | 10 | de |
jgu.pages.start | 3184 | de |
jgu.pages.end | 3196 | de |
jgu.publisher.year | 2014 | - |
jgu.publisher.name | Impact Journals LLC | de |
jgu.publisher.place | S.l. | de |
jgu.publisher.uri | http://dx.doi.org/10.18632/oncotarget.1899 | de |
jgu.publisher.issn | 1949-2553 | de |
jgu.organisation.place | Mainz | - |
jgu.identifier.pmid | 24833526 | - |
jgu.subject.ddccode | 610 | de |
opus.date.modified | 2018-08-08T08:52:45Z | - |
opus.subject.dfgcode | 00-000 | - |
opus.organisation.string | FB 04: Medizin: Institut für Toxikologie | de_DE |
opus.identifier.opusid | 27355 | - |
opus.importsource | pubmed | - |
opus.institute.number | 0414 | - |
opus.metadataonly | false | - |
opus.type.contenttype | Keine | de_DE |
opus.type.contenttype | None | en_EN |
opus.affiliated | Krämer, Oliver | - |
jgu.publisher.doi | 10.18632/oncotarget.1899 | de |
jgu.organisation.ror | https://ror.org/023b0x485 | - |
Appears in collections: | DFG-OA-Publizieren (2012 - 2017) |
Files in This Item:
File | Description | Size | Format | ||
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siah2_antagonizes_tyk2stat3_s-20220915070215809.pdf | 2.31 MB | Adobe PDF | View/Open |