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. 2020 Nov 25;11:609948. doi: 10.3389/fimmu.2020.609948

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Copyright © 2020 Noe and Mitchell

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Mechanisms of MIF signal transduction. Paracrine/autocrine extracellular MIF or endogenously produced cytosolic MIF functionally interacts with cytosolic Jab1/CSN5 resulting in differential cullin-ring ligase (CRL) substrate proteasomal degradation and/or c-Jun phosphorylation/AP-1 activation. Extracellular MIF independently interacts with CD74 in hetero-complex with CD44, CXCR2, CXCR4, and/or CXCR7 to initiate downstream MAPK and/or PI3K pathway effectors.