Identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a repressor of C/EBPbeta-mediated gene activation.
Transcription factor C/EBPbeta 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/EBPbeta is through protein-protein interaction with other transcription factors. Here we report the identification and characterization of physical and functional interactions between C/EBPbeta and heterogeneous nuclear ribonucleoprotein (hnRNP) K. This interaction results in the repression of C/EBPbeta-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/EBPbeta to its cognate DNA site. Furthermore, agp gene activation by the synergistic interaction of Nopp140 and C/EBPbeta is abolished by hnRNP K. The kinetics of appearance of C/EBPbeta-hnRNP K complex in the nuclear extract after initiation of acute-phase reaction indicates that hnRNP K functions as a negative regulator of C/EBPbeta-mediated activation of agp gene.
Miau
L H
LH
Institute of Molecular Medicine, Dr. H.-L. Tsai Memorial Laboratory, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chang
C J
CJ
Shen
B J
BJ
Tsai
W H
WH
Lee
S C
SC
D000595:Amino Acid Sequence; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D002846:Chromatography, Affinity; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007700:Kinetics; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D051381:Rats; D012097:Repressor Proteins / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism*; D015533:Transcriptional Activation
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; D012261:Ribonucleoproteins