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- DOI: 10.1096/fj.09-139998
- PMID: 20086048
- UKPMCID: 20086048
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Interferon-inducible factor 16 is a novel modulator of glucocorticoid action.
Berry, A; Matthews, L; Jangani, M; Plumb, J; Farrow, S; Buchan, N; Wilson, P A; Singh, D; Ray, D W; Donn, R P
The FASEB journal. 2010;24(6):1700.
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Full-text held externally
- DOI: 10.1096/fj.09-139998
- PMID: 20086048
- UKPMCID: 20086048
Abstract
Previously, we used cDNA expression profiling to identify genes associated with glucocorticoid (Gc) sensitivity. We now identify which of these directly influence Gc action. Interferon-inducible protein 16 (IFI16), bone morphogenetic protein receptor type II (BMPRII), and regulator of G-protein signaling 14 (RGS14) increased Gc transactivation, whereas sialyltransferase 4B (SIAT4B) had a negative effect. Amyloid beta (A4) precursor-protein binding, family B, member 1 (APBB1/Fe65) and neural cell expressed developmentally down-regulated 9 (NEDD9) were without effect. Only IFI16 potentiated Gc repression of NF-kappaB. In addition, IFI16 affected basal expression, and Gc induction of endogenous target genes. IFI16 did not affect glucocorticoid receptor (GR) expression, ligand-dependent repression of GR expression, or the ligand-dependent induction of GR phosphorylation on Ser-211 or Ser-203. Coimmunoprecipitation revealed an interaction, suggesting that IFI16 modulation of GR function is mediated by protein crosstalk. Transfection analysis with GR mutants showed that the ligand-binding domain of GR binds IFI16 and is the target domain for IFI16 regulation. Analysis of human lung sections identified colocalization of GR and IFI16, suggesting a physiologically relevant interaction. We demonstrate that IFI16 is a novel modulator of GR function and show the importance of analyzing variation in Gc sensitivity in humans, using appropriate technology, to drive discovery.
Bibliographic metadata
- 082979, Wellcome Trust, United Kingdom
- 16404, Arthritis Research Campaign, United Kingdom
- 17552, Arthritis Research Campaign, United Kingdom
- 17552, Arthritis Research Campaign, United Kingdom
- 17900, Arthritis Research Campaign, United Kingdom
- , Biotechnology and Biological Sciences Research Council, United Kingdom
- , Medical Research Council, United Kingdom
- , Wellcome Trust, United Kingdom