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Title 

Macrophage migration inhibitory factor interacts with thioredoxin-interacting protein and induces NF-κB activity

Authors 

Mi Jeong KimWon Sam KimDong Oh KimJae-Eun ByunH HuySoo Yun LeeHae Young SongYoung-Jun ParkTae-Don KimSuk Ran YoonE J ChoiH HaHaiyoung JungIn Pyo Choi

Publisher 

Elsevier

Issue Date 

2017

Citation 

Cellular Signalling

Keywords 

HDACHeLa cellMIFNF-κBTXNIP

Abstract 

The nuclear factor kappa B (NF-κB) pathway is pivotal in controlling survival and apoptosis of cancer cells. Macrophage migration inhibitory factor (MIF), a cytokine that regulates the immune response and tumorigenesis under inflammatory conditions, is upregulated in various tumors. However, the intracellular functions of MIF are unclear. In this study, we found that MIF directly interacted with thioredoxin-interacting protein (TXNIP), a tumor suppressor and known inhibitor of NF-κB activity, and MIF significantly induced NF-κB activation. MIF competed with TXNIP for NF-κB activation, and the intracellular MIF induced NF-κB target genes, including c-IAP2, Bcl-xL, ICAM-1, MMP2 and uPA, by inhibiting the interactions between TXNIP and HDACs or p65. Furthermore, we identified the interaction motifs between MIF and TXNIP via site-directed mutagenesis of their cysteine (Cys) residues. Cys57 and Cys81 of MIF and Cys36 and Cys120 of TXNIP were responsible for the interaction. MIF reversed the TXNIP-induced suppression of cell proliferation and migration. Overall, we suggest that MIF induces NF-κB activity by counter acting the inhibitory effect of TXNIP on the NF-κB pathway via direct interaction with TXNIP. These findings reveal a novel intracellular function of MIF in the progression of cancer.

ISSN 

0898-6568

Link 

http://dx.doi.org/10.1016/j.cellsig.2017.03.007

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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