Interferons Transcriptionally Up-Regulate MLKL Expression in Cancer Cells
| Autor: | Sjoerd J L van Wijk, Anne-Kathrin Knuth, Stefanie Rösler, Barbara Schenk, Lisa Kowald, Simone Fulda |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research NSA necrosulfonamide GAPDH glyceraldehyde 3-phosphate dehydrogenase 0302 clinical medicine Interferon Neoplasms AML acute myeloid leukemia Regulation of gene expression Gene knockdown ns non-silencing lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell biology Gene Expression Regulation Neoplastic STAT signal transducer and activator of transcription STAT1 Transcription Factor Caspases 030220 oncology & carcinogenesis pSTAT1 phospho-STAT1 JAK Janus kinase medicine.drug Transcriptional Activation Original article TNFα tumor necrosis factor alpha Biology DSMZ Deutsche Sammlung von Mikroorganismen und Zellkulturen lcsh:RC254-282 PI propidium iodide 03 medical and health sciences Cell Line Tumor IRF1 IFN-regulatory factor 1 medicine Humans IFN interferon ddc:610 RNA Messenger RIPK receptor-interacting protein kinase MLKL mixed-lineage kinase domain-like Transcription factor zVAD.fmk N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone FDA Food and Drug Administration MEF mouse embryonic fibroblast 030104 developmental biology IRF1 Cancer cell STAT protein ISG IFN-stimulated gene Interferons FCS fetal calf serum Janus kinase Protein Kinases Interferon Regulatory Factor-1 |
| Zdroj: | Neoplasia: An International Journal for Oncology Research, Vol 21, Iss 1, Pp 74-81 (2019) Neoplasia (New York, N.Y.) |
| ISSN: | 1476-5586 |
| Popis: | Interferons (IFNs) are key players in the tumor immune response and act by inducing the expression of IFN-stimulated genes (ISGs). Here, we identify the mixed-lineage kinase domain-like pseudokinase (MLKL) as an ISG in various cancer cell lines. Both type I and type II IFNs increase the expression of MLKL indicating that MLKL up-regulation is a general feature of IFN signaling. IFNγ up-regulates mRNA as well as protein levels of MLKL demonstrating that IFNγ transcriptionally regulates MLKL. This notion is further supported by Actinomycin D chase experiments showing that IFNγ-stimulated up-regulation of MLKL is prevented in the presence of the transcriptional inhibitor Actinomycin D. Also, knockdown of the transcription factor IFN-regulatory factor 1 (IRF1) and signal transducer and activator of transcription (STAT) 1 as well as knockout of IRF1 significantly attenuate IFNγ-mediated induction of MLKL mRNA levels. Up-regulation of MLKL by IFNγ provides a valuable tool to sensitize cells towards necroptotic cell death and to overcome apoptosis resistance of cancer cells. |
| Databáze: | OpenAIRE |
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