Macrophage migration inhibitory factor does not modulate co-activation of androgen receptor by Jab1/CSN5.
Macrophage migration inhibitory factor (MIF) is a pro-inflammatory 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 non-receptor mediated endocytosis. Endocytosed or endogenous MIF interacts with Jun activation domain-binding protein 1 (Jab1), originally described as transcriptional co-activator for the transcription factor AP-1, that is also known as subunit 5 of the COP9 signalosome (CSN5). Since Jab1/CSN5 also functions as a co-activator 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 phospho-c-Jun levels by TNFalpha and PMA and, hence, is biologically active, but (iii) is not able to interfere with co-activation by Jab1/CSN5 of the androgen receptor.
Berndt
Kersten
K
Institut für Anatomie und Zellbiologie, Justus-Liebig-Universität Giessen, Aulweg 123, 35385, Giessen, Germany.
Kim
Marcus
M
Meinhardt
Andreas
A
Klug
Jörg
J
D000818:Animals; D000075686:COP9 Signalosome Complex; D004705:Endocytosis; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology