Interferons Transcriptionally Up-Regulate MLKL Expression in Cancer Cells.

Caspases / metabolism Cell Line, Tumor Gene Expression Regulation, Neoplastic / drug effects Humans Interferon Regulatory Factor-1 / metabolism Interferons / metabolism Neoplasms / genetics Protein Kinases / genetics RNA, Messenger / genetics STAT1 Transcription Factor / metabolism Transcriptional Activation / drug effects

Journal

Neoplasia (New York, N.Y.)
ISSN: 1476-5586
Titre abrégé: Neoplasia
Pays: United States
ID NLM: 100886622

Informations de publication

Date de publication:
01 2019
Historique:
received: 06 08 2018
revised: 07 11 2018
accepted: 09 11 2018
pubmed: 7 12 2018
medline: 12 2 2019
entrez: 7 12 2018
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.neo.2018.11.002 PMID: 30521981 PMC: PMC6310689
pubmed: 30521981
pii: S1476-5586(18)30436-6
doi: 10.1016/j.neo.2018.11.002
pmc: PMC6310689
pii:
doi:

Substances chimiques

IRF1 protein, human 0
Interferon Regulatory Factor-1 0
RNA, Messenger 0
STAT1 Transcription Factor 0
STAT1 protein, human 0
Interferons 9008-11-1
MLKL protein, human EC 2.7.-
Protein Kinases EC 2.7.-
Caspases EC 3.4.22.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

74-81

Informations de copyright

Copyright © 2018. Published by Elsevier Inc.

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Auteurs

Anne-Kathrin Knuth (AK)

Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt, Germany.

Stefanie Rösler (S)

Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt, Germany.

Barbara Schenk (B)

Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt, Germany.

Lisa Kowald (L)

Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt, Germany.

Sjoerd J L van Wijk (SJL)

Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt, Germany.

Simone Fulda (S)

Institute for Experimental Cancer Research in Pediatrics, Goethe-University, Frankfurt, Germany; German Cancer Consortium (DKTK), Partner Site, Frankfurt, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: simone.fulda@kgu.de.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines régulatrices de l'apoptose › Caspases › Interferons Transcriptionally Up-Regulate MLKL...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › Interferons Transcriptionally Up-Regulate MLKL...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Interferons Transcriptionally Up-Regulate MLKL...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Interferons Transcriptionally Up-Regulate MLKL...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de régulation d'interféron › Facteur-1 de régulation d'interféron › Interferons Transcriptionally Up-Regulate MLKL...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interférons › Interferons Transcriptionally Up-Regulate MLKL...
questionsmedicales.fr › Tumeurs › Interferons Transcriptionally Up-Regulate MLKL...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Phosphotransferases (Alcohol Group Acceptor) › Protein kinases › Interferons Transcriptionally Up-Regulate MLKL...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Interferons Transcriptionally Up-Regulate MLKL...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteurs de transcription STAT › Facteur de transcription STAT-1 › Interferons Transcriptionally Up-Regulate MLKL...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Activation de la transcription › Interferons Transcriptionally Up-Regulate MLKL...