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.