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
Full text not available from this repository.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 | ||||||||||||||||||||
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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 | ||||||||||||||||||||
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Refereed: | Yes | ||||||||||||||||||||
URI: | http://kups.ub.uni-koeln.de/id/eprint/24727 |
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