Overexpression of the transcription factor Sp1 activates the OAS-RNAse L-RIG-I pathway

PloS One
Valéryane Dupuis-MaurinMarie-Cécile Michallet

Abstract

Deregulated expression of oncogenes or transcription factors such as specificity protein 1 (Sp1) is observed in many human cancers and plays a role in tumor maintenance. Paradoxically in untransformed cells, Sp1 overexpression induces late apoptosis but the early intrinsic response is poorly characterized. In the present work, we studied increased Sp1 level consequences in untransformed cells and showed that it turns on an early innate immune transcriptome. Sp1 overexpression does not activate known cellular stress pathways such as DNA damage response or endoplasmic reticulum stress, but induces the activation of the OAS-RNase L pathway and the generation of small self-RNAs, leading to the upregulation of genes of the antiviral RIG-I pathway at the transcriptional and translational levels. Finally, Sp1-induced intrinsic innate immune response leads to the production of the chemokine CXCL4 and to the recruitment of inflammatory cells in vitro and in vivo. Altogether our results showed that increased Sp1 level in untransformed cells constitutes a novel danger signal sensed by the OAS-RNase L axis leading to the activation of the RIG-I pathway. These results suggested that the OAS-RNase L-RIG-I pathway may be activated in sterile ...Continue Reading

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Citations

Jan 14, 2016·International Journal of Molecular Sciences·Heather J EzelleBret A Hassel
Mar 17, 2016·BMC Immunology·Jun YangLouis M Cosentino
Aug 2, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·LaTeira D HaynesCatherine C Hedrick
Feb 14, 2020·International Journal of Molecular Sciences·Balachandar VellingiriSsang-Goo Cho
Oct 24, 2020·Methods : a Companion to Methods in Enzymology·Hao WangJianrong Wang

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Datasets Mentioned

BETA
E-MEXP-1702

Methods Mentioned

BETA
ubiquitination
Profiler
FCS
flow cytometry
transfection
PCR
electrophoresis
fluorescence microscopy
ELISA

Software Mentioned

gProfileR
Profiler
StepOne +
limma
oPOSSUM
ImageJ
FlowJo
affy
R
: Profiler

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