FIG. 1. Model of positive and negative signaling to the interferon regulatory factor-1 (IRF-1) gene. (A) A number of mediators positively regulate prolactin (PRL) stimulation of IRF-1 gene transcription. These include PRL-inducible Stat1, the constitutive factor Sp1, and the coactivator p300/CBP, which enhances Stat1 activation of the IRF-1 promoter. (B) PRL-inducible Stat5 inhibits IRF-1 transcription. Although competition for the coactivator p300/CBP appears to be involved (Luo and Yu-Lee, 1997,2000), the in vivo mechanism of inhibition at the IRF-1 promoter is as yet unclear. (C) The IRF-1 promoter can be activated via PRL-inducible Stat1 as well as by tumor necrosis factor alpha (TNF
)-inducible nuclear factor kappa B (NF
B) binding to their respective response elements. In this model of positive and negative cytokine signal cross talk, Stat1 synergizes with NFB but Stat5 antagonizes NFB signaling to the IRF-1 promoter. Additional factors that can be recruited by Stats or NFB to regulate IRF-1 promoter activity are indicated in gray.
