Schroeder, Linda, Herwartz, Christine, Jordanovski, Darko and Steger, Gertrud (2017). ZNF395 Is an Activator of a Subset of IFN-Stimulated Genes. Mediat. Inflamm., 2017. LONDON: HINDAWI LTD. ISSN 1466-1861

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Abstract

Activation of the interferon (IFN) pathway in response to infection with pathogens results in the induction of IFN-stimulated genes (ISGs) including proinflammatory cytokines, which mount the proper antiviral immune response. However, aberrant expression of these genes is pathogenic to the host. In addition to IFN-induced transcription factors non-IFN-regulated factors contribute to the transcriptional control of ISGs. Here, we show by genome wide expression analysis, siRNA-mediated suppression and Doxycycline-induced overexpression that the cellular transcription factor ZNF395 activates a subset of ISGs including the chemokines CXCL10 and CXCL11 in keratinocytes. We found that ZNF395 acts independently of IFN but enhances the IFN-induced expression of CXCL10 and CXCL11. Luciferase reporter assays revealed a requirement of intact NF.. B-binding sites for ZNF395 to stimulate the CXCL10 promoter. The transcriptional activation of CXCL10 and CXCL11 by ZNF395 was abolished after inhibition of IKKby BMS-345541, which increased the stability of ZNF395. ZNF395 encodes at least two motifs that mediate the enhanced degradation of ZNF395 in response to IKK activation. Thus, IKK is required for ZNF395-mediated activation of transcription and enhances its turn-over to keep the activity of ZNF395 low. Our results support a previously unrecognized role of ZNF395 in the innate immune response and inflammation.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Schroeder, LindaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Herwartz, ChristineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jordanovski, DarkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steger, GertrudUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-247277
DOI: 10.1155/2017/1248201
Journal or Publication Title: Mediat. Inflamm.
Volume: 2017
Date: 2017
Publisher: HINDAWI LTD
Place of Publication: LONDON
ISSN: 1466-1861
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NF-KAPPA-B; PAPILLOMAVIRUS BINDING-FACTOR; BETA-TRCP; CXCR3; IDENTIFICATION; HYPOXIA; EXPRESSION; CELLS; TRANSCRIPTION; MECHANISMSMultiple languages
Cell Biology; ImmunologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/24727

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