Transcriptional induction of the alpha-1 acid glycoprotein (AGP) gene by synergistic interaction of two alternative activator forms of AGP/enhancer-binding protein (C/EBP beta) and NF-kappaB or Nopp140.
Alpha-1 acid glycoprotein/enhancer-binding protein (AGP/EBP) (C/EBPbeta), a member of the C/EBP family, is one of the key transcription factors responsible for the induction of a wide array of genes, some of which are expressed during the acute-phase response. Both activator and repressor were shown to be encoded by the intronless agp/ebp or its rat and human homologs, which contain a common bZIP domain at their C-terminal regions. Expression of the AGP gene (agp) is regulated by AGP/EBP in liver during the acute-phase response. However, the molecular mechanism for this regulation is poorly understood. The experiments reported here demonstrate that two activator forms of AGP/EBP, one of which has an additional 21 amino acids at its N-terminal region, are expressed in liver as well as in a number of cell lines. We have also demonstrated that NF-kappaB and a phosphoprotein of 140 kDa, Nopp140, interact with different AGP/EBP activators synergistically, which results in induction of the agp gene in an AGP/EBP-binding-motif-dependent manner. Furthermore, extracellular stimuli that are known to be NF-kappaB inducers can selectively activate the agp gene by cooperating with one of the two activator forms of AGP/EBP. The physiological significance of differential regulation for the function of two activator forms of AGP/EBP through selective interaction with different transcription factors is discussed.
Lee
Y M
YM
Institute of Biological Chemistry, National Taiwan University, Taipei.
Miau
L H
LH
Chang
C J
CJ
Lee
S C
SC
D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins; D017931:DNA Primers / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D005786:Gene Expression Regulation; D005796:Genes; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000502:physiology*; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D009961:Orosomucoid / Q000235:genetics*; D010750:Phosphoproteins / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D022762:CCAAT-Enhancer-Binding Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D016328:NF-kappa B; C075564:NOLC1 protein, human; C513068:Nolc1 protein, mouse; C513067:Nolc1 protein, rat; D009687:Nuclear Proteins; D009961:Orosomucoid; D010750:Phosphoproteins; D012333:RNA, Messenger