2. Academic Validation
  3. Macrophage migration inhibitory factor interacts with thioredoxin-interacting protein and induces NF-κB activity

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

  • Cell Signal. 2017 Jun:34:110-120. doi: 10.1016/j.cellsig.2017.03.007.
Mi Jeong Kim 1,  Won Sam Kim 1,  Dong Oh Kim 1,  Jae-Eun Byun 2,  Hangsak Huy 1,  Soo Yun Lee 3,  Hae Young Song 3,  Young-Jun Park 1,  Tae-Don Kim 1,  Suk Ran Yoon 1,  Eun-Ji Choi 4,  Hyunjung Ha 5,  Haiyoung Jung 6,  Inpyo Choi 7
Affiliations

Affiliations

  • 1 Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea.
  • 2 Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea; Department of Biochemistry, School of Life Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea.
  • 3 Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea.
  • 4 Department of Hematology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea.
  • 5 Department of Biochemistry, School of Life Sciences, Chungbuk National University, Cheongju 28644, Republic of Korea.
  • 6 Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea. Electronic address: [email protected].
  • 7 Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong-gu, Daejeon 34141, Republic of Korea; Department of Functional Genomics, University of Science and Technology, Yuseong-gu, Daejeon 34113, Republic of Korea. Electronic address: [email protected].
PMID: 28323005 DOI: 10.1016/j.cellsig.2017.03.007
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.

Keywords

HDAC; HeLa cell; MIF; NF-κB; TXNIP.

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