Authors: Kersten Berndt Marcus Kim Andreas Meinhardt Jörg Klug
Publish Date: 2007/09/05
Volume: 307, Issue: 1-2, Pages: 265-271
Abstract
Macrophage migration inhibitory factor MIF is a proinflammatory immune modulator that plays an important role in the regulation of innate and adaptive immune responses MIF signaling involves CD74/CD44 membrane receptor complexes the chemokine receptors CXCR2 and 4 as well as uptake by nonreceptor mediated endocytosis Endocytosed or endogenous MIF interacts with Jun activation domainbinding protein 1 Jab1 originally described as transcriptional coactivator for the transcription factor AP1 that is also known as subunit 5 of the COP9 signalosome CSN5 Since Jab1/CSN5 also functions as a coactivator for a number of steroid hormone receptors SHRs it had been speculated that MIF could modulate Jab1/CSN5–SHR interactions Here we show i that fluorescently labeled MIF is internalized by NIH 3T3 cells within minutes ii compromises the induction of phosphocJun levels by TNFα and PMA and hence is biologically active but iii is not able to interfere with coactivation by Jab1/CSN5 of the androgen receptorWe thank Suada Fröhlich Tamara Henke and Eva Schneider for expert technical assistance Jürgen Bernhagen for providing pCIneoJab1 and fruitful discussions Aria Baniahmad for pSG5hAR Jan Trapman for pPSA61Luc and the Schering AG Berlin for generous support KB received a scholarship from the Graduiertenkolleg 533 “CellCellInteraction in Reproduction”
Keywords: