| First Author | Alam T | Year | 1992 |
| Journal | Biochemistry | Volume | 31 |
| Issue | 7 | Pages | 1928-36 |
| PubMed ID | 1371400 | Mgi Jnum | J:2980 |
| Mgi Id | MGI:51496 | Doi | 10.1021/bi00122a005 |
| Citation | Alam T, et al. (1992) Interaction of acute-phase-inducible and liver-enriched nuclear factors with the promoter region of the mouse alpha 1-acid glycoprotein gene-1. Biochemistry 31(7):1928-36 |
| abstractText | The synthesis and secretion of several acute-phase proteins increases markedly following physiological stress. alpha 1-Acid glycoprotein (AGP), a major acute-phase reactant made by the liver, is strongly induced by inflammatory agents such as lipopolysaccharide (LPS). Nuclear run-on assay showed a 17-fold increase in the rate of AGP transcription 4 h following LPS injection. DNase I footprinting assays revealed multiple protein binding domains in the mouse AGP-1 promoter region. Region B (-104 to -91) is protected by a liver-enriched transcription factor that is heat labile and in limiting quantity. An adjacent region, C (-125 to -104), is well-protected by nuclear extracts from hepatocytes. Electrophoretic mobility shift assays indicated that only one DNA-protein complex can form with an oligonucleotide corresponding to region B. However, nuclear proteins from untreated mouse liver can form three strong complexes (C1, C2, and C3) and a weak one (C4) with oligonucleotide C. An acute-phase-inducible DNA-binding protein (AP-DBP) forms complex 4. A dramatic increase (over 11-fold) in AP-DBP binding activity is seen with nuclear proteins from LPS-stimulated animals. Interestingly, AP-DBP, a heat-stable factor, can form heterodimers with the transcription factor CCAAT/enhancer binding protein (C/EBP). Furthermore, purified C/EBP also binds avidly to region C. Our studies indicate that several liver-enriched nuclear factors can interact with AGP-1 promoter and that AP-DBP binds to the AGP-1 promoter with high affinity only during the acute-phase induction. |
