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Cell Rep. 2016 Oct 4;17(2):425-435. doi: 10.1016/j.celrep.2016.09.009.

Association of a Network of Interferon-Stimulated Genes with a Locus Encoding a Negative Regulator of Non-conventional IKK Kinases and IFNB1.

Author information

1
Cardiovascular Biology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada; Département de Médecine, Faculté de Médecine, Université de Montréal, Montréal, QC J2S 2M2, Canada.
2
Département de Médecine, Faculté de Médecine, Université de Montréal, Montréal, QC J2S 2M2, Canada; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CR-CHUM), Montréal, QC H2X 3J4, Canada.
3
Cardiovascular Biology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada.
4
Cardiovascular Biology Research Unit, Institut de Recherches Cliniques de Montréal (IRCM), Montréal, QC H2W 1R7, Canada; Département de Médecine, Faculté de Médecine, Université de Montréal, Montréal, QC J2S 2M2, Canada. Electronic address: deschec@ircm.qc.ca.

Abstract

Functional genomic analysis of gene expression in mice allowed us to identify a quantitative trait locus (QTL) linked in trans to the expression of 190 gene transcripts and in cis to the expression of only two genes, one of which was Ypel5. Most of the trans-expression QTL genes were interferon-stimulated genes (ISGs), and their expression in mouse macrophage cell lines was stimulated in an IFNB1-dependent manner by Ypel5 silencing. In human HEK293T cells, YPEL5 silencing enhanced the induction of IFNB1 by pattern recognition receptors and phosphorylation of TBK1/IKBKE kinases, whereas co-immunoprecipitation experiments revealed that YPEL5 interacted physically with IKBKE. We thus found that the Ypel5 gene (contained in a locus linked to a network of ISGs in mice) is a negative regulator of IFNB1 production and innate immune responses that interacts functionally and physically with TBK1/IKBKE kinases.

PMID:
27705791
DOI:
10.1016/j.celrep.2016.09.009
[Indexed for MEDLINE]
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