IRF2BP2 Modulates the Crosstalk between Glucocorticoid and TNF Signaling
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CitationKaiser Manjur, ABM. Lempiäinen, Joanna K. Malinen, Marjo. Palvimo, Jorma J. Niskanen, Einari A. (2019). IRF2BP2 Modulates the Crosstalk between Glucocorticoid and TNF Signaling. Journal of steroid biochemistry and molecular biology, 192, 105382. 10.1016/j.jsbmb.2019.105382.
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 α (TNF), including metabolic and inflammatory pathways. Taken together, our data support the role of IRF2BP2 as a coregulator of both GR and NF-κB, potentially modulating the crosstalk between GC and TNF signaling.