Post-translational regulation of macrophage migration inhibitory factor: Basis for functional fine-tuning

• Published in: Redox biology Vol. 15; no. C; pp. 135 - 142
• Main Authors: Schindler, Lisa, Dickerhof, Nina, Hampton, Mark B., Bernhagen, Jürgen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2018; Elsevier
• Subjects: Amino Acid Sequence - genetics; Animals; Antigens, Differentiation, B-Lymphocyte - genetics; Carbamylation; Cysteine - metabolism; Cytokine; Histocompatibility Antigens Class II - genetics; Humans; Inflammation; Macrophage Migration-Inhibitory Factors - genetics; Macrophage Migration-Inhibitory Factors - metabolism; Myeloperoxidase; N-terminal proline; Oxidation-Reduction; OxMIF; Post-translational modification; Protein Conformation; Protein Processing, Post-Translational - genetics; Redox regulation; Review; Tautomerase; Carbamylation; Post-translational modification; GIF; Cytokine; Redox regulation; Inflammation; MIF; MPO; N-terminal proline; OxMIF; TPOR; Myeloperoxidase; Tautomerase
• ISSN: 2213-2317; 2213-2317
• DOI: 10.1016/j.redox.2017.11.028

Macrophage migration inhibitory factor (MIF) is a chemokine-like protein and an important mediator in the inflammatory response. Unlike most other pro-inflammatory cytokines, a number of cell types constitutively express MIF and secretion occurs from preformed stores. MIF is an evolutionarily conserved protein that shows a remarkable functional diversity, including specific binding to surface CD74 and chemokine receptors and the presence of two intrinsic tautomerase and oxidoreductase activities. Several studies have shown that MIF is subject to post-translational modification, particularly redox-dependent modification of the catalytic proline and cysteine residues. In this review, we summarize and discuss MIF post-translational modifications and their effects on the biological properties of this protein. We propose that the redox-sensitive residues in MIF will be modified at sites of inflammation and that this will add further depth to the functional diversity of this intriguing cytokine. •MIF is a pro-inflammatory cytokine with tautomerase and oxidoreductase activity.•MIF is susceptible to post-translational modifications, including redox modification.•Oxidants and electrophiles generated at inflammatory sites can modify MIF.•The biological consequences of redox modification need detailed characterization.