Figure 1.

Schematic showing mechanisms controlling MIF transcription. (A) Control of the MIF promoter according to Roger et al.¹⁴. Microbial pathogens induce the phosphorylation, nuclear accumulation and DNA binding activity of Sp1, which acts together with cAMP response element binding protein (CREB) as positive regulators of human MIF gene expression. (B) Under Hypoxia, MIF gene expression is driven by hypoxia-inducible factor-1α (HIF-1α), and this process is enhanced by hypoxia-mediated CREB degradation, whereas under normoxia, this effect is suppressed by CREB¹³. (C) IKK-α-mediated phosphorylation of steroid receptor coactivator-3 (SRC-3) at Ser857 is responsible for the recruitment of CREB binding protein (CBP) and the co-activation of HIF-1α to induce the gene expression of MIF. Expressed MIF protein in turn inhibits autophagic cell death, favoring the proliferation and survival of breast tumor cells. Ub, ubiquitin.