Macrophage migration inhibitory factor does not modulate co-activation of androgen receptor by Jab1/CSN5

Mol Cell Biochem. 2008 Jan;307(1-2):265-71. doi: 10.1007/s11010-007-9578-3. Epub 2007 Sep 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COP9 Signalosome Complex
  • Endocytosis
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Macrophage Migration-Inhibitory Factors / metabolism
  • Macrophage Migration-Inhibitory Factors / physiology*
  • Mice
  • NIH 3T3 Cells
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism
  • Peptide Hydrolases / physiology*
  • Proto-Oncogene Proteins c-jun / metabolism
  • Receptors, Androgen / metabolism*
  • Recombinant Proteins / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology
  • Time Factors
  • Transcription Factors / physiology
  • Transcriptional Activation*
  • Tumor Necrosis Factor-alpha / pharmacology


  • Intracellular Signaling Peptides and Proteins
  • Macrophage Migration-Inhibitory Factors
  • Proto-Oncogene Proteins c-jun
  • Receptors, Androgen
  • Recombinant Proteins
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Peptide Hydrolases
  • Cops5 protein, mouse
  • COP9 Signalosome Complex
  • Tetradecanoylphorbol Acetate