Identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a repressor of C/EBPβ-mediated gene activation

Transcription factor C/EBP beta has been known to regulate a wide array of genes including those involved in the acute-phase response. One of the molecular mechanisms underlying transcription activation by C/EBP beta is through protein-protein interaction with other transcription factors. Here we report the identification and characterization of physical and functional interactions between C/EBP beta and heterogeneous nuclear ribonucleoprotein (hnRNP) K. This interaction results in the repression of C/EBP beta-dependent trans-activation of the agp gene. Footprinting assays indicate that hnRNP K cannot bind to the promoter region of agp gene or interfere with the binding of C/EBP beta to its cognate DNA site. Furthermore, agp gene activation by the synergistic interaction of Nopp140 and C/EBP beta is abolished by hnRNP K. The kinetics of appearance of C/EBP beta-hnRNP It complex in the nuclear extract after initiation of acute-phase reaction indicates that hnRNP K functions as a negative regulator of C/EBP beta-mediated activation of agp gene.