Interferons transcriptionally up-regulate MLKL expression in cancer cells
- 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.
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| Author: | Anne-Kathrin Knuth, Stefanie Rösler, Barbara SchenkGND, Lisa Kowald, Sjoerd van WijkORCiDGND, Simone FuldaORCiDGND |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-492031 |
| DOI: | https://doi.org/10.1016/j.neo.2018.11.002 |
| ISSN: | 1522-8002 |
| ISSN: | 1476-5586 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/30521981 |
| Parent Title (English): | Neoplasia |
| Publisher: | Stockton Press |
| Place of publication: | Basingstoke |
| Document Type: | Article |
| Language: | English |
| Year of Completion: | 2018 |
| Date of first Publication: | 2018/12/03 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2019/03/21 |
| Volume: | 21 |
| Issue: | 1 |
| Page Number: | 8 |
| First Page: | 74 |
| Last Page: | 81 |
| Note: | © 2018 Published by Elsevier Inc. on behalf of Neoplasia Press, Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
| HeBIS-PPN: | 448050161 |
| Institutes: | Medizin / Medizin |
| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - Namensnennung-Nicht kommerziell - Keine Bearbeitung 4.0 |
