IRF2BP2 modulates the crosstalk between glucocorticoid and TNF signaling

A B M Kaiser Manjur; Joanna K Lempiäinen; Marjo Malinen; Jorma J Palvimo; Einari A Niskanen

doi:10.1016/j.jsbmb.2019.105382

IRF2BP2 modulates the crosstalk between glucocorticoid and TNF signaling

J Steroid Biochem Mol Biol. 2019 Sep:192:105382. doi: 10.1016/j.jsbmb.2019.105382. Epub 2019 May 28.

Authors

A B M Kaiser Manjur¹, Joanna K Lempiäinen¹, Marjo Malinen², Jorma J Palvimo³, Einari A Niskanen⁴

Affiliations

¹ Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland.
² Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland; Department of Environmental and Biological Sciences, University of Eastern Finland, Joensuu, Finland.
³ Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. Electronic address: [email protected].
⁴ Institute of Biomedicine, University of Eastern Finland, Kuopio, Finland. Electronic address: [email protected].

PMID: 31145973
DOI: 10.1016/j.jsbmb.2019.105382

Abstract

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.

Keywords: Dexamethasone; Glucocorticoid receptor (GR); Interferon regulatory factor-2 binding protein-2 (IRF2BP2); Nuclear factor-κB (NF-κB); Tumor necrosis factor α (TNF).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Anti-Inflammatory Agents / pharmacology*
Cell Movement
Cell Proliferation
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Gene Expression Regulation / drug effects*
Glucocorticoids / pharmacology*
HEK293 Cells
Humans
Inflammation / genetics
Inflammation / metabolism
Inflammation / pathology
Inflammation / prevention & control*
NF-kappa B / genetics
NF-kappa B / metabolism
Transcription Factors / genetics
Transcription Factors / metabolism*
Tumor Necrosis Factor-alpha / pharmacology*

Substances

Anti-Inflammatory Agents
DNA-Binding Proteins
Glucocorticoids
IRF2BP2 protein, human
NF-kappa B
Transcription Factors
Tumor Necrosis Factor-alpha