Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 192, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2019.105382
Keywords
Glucocorticoid receptor (GR); Interferon regulatory factor-2 binding protein-2(IRF2BP2); Nuclear factor-kappa B (NF-kappa B); Dexamethasone; Tumor necrosis factor alpha (TNF)
Funding
- Academy of Finland
- Cancer Foundation Finland
- Sigrid Juselius Foundation
- UEF Doctoral Programme in Molecular Medicine
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IRF2BP2 (interferon regulatory factor-2 binding protein-2) is an uncharacterized interaction partner of glucocorticoid (GC) receptor (GR), an anti-inflammatory and metabolic transcription factor. Here, we show that GC changes the chromatin binding of IRF2BP2 in natural chromatin milieu. The GC-induced IRF2BP2-binding sites co-occur with GR binding sites and are associated with GC-induced genes. Moreover, the depletion of IRF2BP2 modulates transcription of GC-regulated genes, represses cell proliferation and increases cell movement in HEK293 cells. In A549 cells, the depletion extensively alters the responses to GC and tumor necrosis factor alpha (TNF), including metabolic and inflammatory pathways. Taken together, our data support the role of IRF2BP2 as a coregulator of both GR and NF-kappa B potentially modulating the crosstalk between GC and TNF signaling.
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