TY  - JOUR
A1  - Knuth, Anne-Kathrin
A1  - Rösler, Stefanie
A1  - Schenk, Barbara
A1  - Kowald, Lisa
A1  - Wijk, Sjoerd van
A1  - Fulda, Simone
T1  - Interferons transcriptionally up-regulate MLKL expression in cancer cells
T2  - Neoplasia
N2  - 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.
Y1  - 2018
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/49203
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-492031
SN  - 1522-8002
SN  - 1476-5586
N1  - © 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/).
VL  - 21
IS  - 1
SP  - 74
EP  - 81
PB  - Stockton Press
CY  - Basingstoke
ER  -