Interaction of acute-phase-inducible and liver-enriched nuclear factors with the promoter region of the mouse alpha sub 1 -acid glycoprotein gene-1

Journal Article · Tue Feb 25 00:00:00 EST 1992 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00122a005· OSTI ID:5562695

Alam, T; Papaconstantinou, J ^[1]

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1. Univ. of Texas Medical Branch, Galveston (United States) Shriners Burns Inst., Galveston, TX (United States)

The synthesis and secretion of several acute-phase proteins increases markedly following physiological stress. {alpha}{sub 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 ({minus}104 to {minus}91) is protected by a liver-enriched transcription factor that is heat labile and in limiting quantity. An adjacent region, C ({minus}125 to {minus}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. The 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.

• OSTI ID: 5562695
• Journal Information: Biochemistry; (United States), Vol. 31:7; ISSN 0006-2960
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
GENES
DNA SEQUENCING
GLYCOPROTEINS
AMINO ACID SEQUENCE
INJURIES
LIPOPOLYSACCHARIDES
LIVER CELLS
PHYSIOLOGY
SECRETION
ANIMAL CELLS
CARBOHYDRATES
LIPIDS
MOLECULAR STRUCTURE
ORGANIC COMPOUNDS
POLYSACCHARIDES
PROTEINS
SACCHARIDES
SOMATIC CELLS
STRUCTURAL CHEMICAL ANALYSIS
550200* - Biochemistry