KRAB-Zinc Finger Protein ZNF268a Deficiency Attenuates the Virus-Induced Pro-Inflammatory Response by Preventing IKK Complex Assembly

Autor:	Wenxin Li, Yucong Lei, Wei Yin, Jingwen Wang, Zan Huang, Guihong Sun, Yi Liu, Mingxiong Guo
Rok vydání:	2019
Předmět:	0301 basic medicine Small interfering RNA THP-1 Cells viruses medicine.medical_treatment IKKα Immunoblotting IκB kinase Real-Time Polymerase Chain Reaction Article 03 medical and health sciences ZNF268 0302 clinical medicine medicine Humans Immunoprecipitation KRAB-ZNF Zinc finger biology Interleukin-6 Tumor Necrosis Factor-alpha HEK 293 cells NF-kappa B General Medicine biology.organism_classification Sendai virus Cell biology I-kappa B Kinase Repressor Proteins 030104 developmental biology Cytokine HEK293 Cells Vesicular stomatitis virus pro-inflammatory cytokine 030220 oncology & carcinogenesis viral infection Signal transduction Signal Transduction
Zdroj:	Cells Volume 8 Issue 12
ISSN:	2073-4409
Popis:	Despite progress in understanding how virus-induced, NF-&kappa B-dependent pro-inflammatory cytokines are regulated, there are still factors and mechanisms that remain to be explored. We aimed to uncover the relationship between KRAB-zinc finger protein ZNF268a and NF-&kappa B-mediated cytokine production in response to viral infection. To this end, we established a ZNF268a-knockout cell line using a pair of sgRNAs that simultaneously target exon 3 in the coding sequence of the ZNF268 gene in HEK293T. HEK293T cells lacking ZNF268a showed less cytokine expression at the transcription and protein levels in response to Sendai virus/vesicular stomatitis virus (SeV/VSV) infection than wild-type cells. Consistent with HEK293T, knock-down of ZNF268a by siRNAs in THP-1 cells significantly dampened the inflammatory response. Mechanistically, ZNF268a facilitated NF-&kappa B activation by targeting IKK&alpha helping to maintain the IKK signaling complex and thus enabling proper p65 phosphorylation and nuclear translocation. Taken together, our data suggest that ZNF268a plays a positive role in the regulation of virus-induced pro-inflammatory cytokine production. By interacting with IKK&alpha ZNF268a promotes NF-&kappa B signal transduction upon viral infection by helping to maintain the association between IKK complex subunits.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2509a45523cf8cafab7e53de8e6159af https://pubmed.ncbi.nlm.nih.gov/31835635 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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