IFN-gamma-stimulated transcriptional activation by IFN-gamma-activated transcriptional element-binding factor 1 occurs via an inducible interaction with CAAAT/enhancer-binding protein-beta.
IFN-gamma-activated transcriptional element (GATE)-binding factor 1 (GBF1) was identified as a transactivator that induces gene expression through GATE, a novel IFN-inducible element. Although it can induce gene expression, it is an extremely weak DNA-binding protein on its own. GATE also binds another transcription factor, C/EBP-beta. Therefore, we explored whether GBF1 physically interacts with C/EBP-beta to induce IFN-gamma-regulated transcription. In response to IFN-gamma, C/EBP-beta undergoes phosphorylation at a critical ERK1/2 phosphorylation motif. Mutational inactivation of this motif and/or interference with the ERK1/2 activation prevented the IFN-gamma-induced interactions between GBF1 and C/EBP-beta. A 37-aa long peptide derived from the GBF1 protein can associate with C/EBP-beta in an IFN-inducible manner. These results identify a converging point for two transactivators that exert their effects through a single response element. Together, our studies identify a novel regulatory mechanism that controls IFN-induced transcription.
Meng
Qingjun
Q
Greenebaum Cancer Center, Department of Microbiology and Immunology, Molecular and Cellular Biology Graduate Program, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Raha
Abhijit
A
Roy
Sanjit
S
Hu
Junbo
J
Kalvakolanu
Dhananjaya V
DV
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D007371:Interferon-gamma / Q000502:physiology*; D019746:Intramolecular Oxidoreductases; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D008969:Molecular Sequence Data; D000071876:Prostaglandin-E Synthases; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D014162:Transfection
D022782:CCAAT-Enhancer-Binding Protein-beta; D007155:Immunologic Factors; D015534:Trans-Activators; D007371:Interferon-gamma; D019950:Mitogen-Activated Protein Kinase 1; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases