NF-AB, a liver-specific and cytokine-inducible nuclear factor that interacts with the interleukin-1 response element of the rat alpha 1-acid glycoprotein gene.
The 142-bp cytokine response element of the rat alpha 1-acid glycoprotein (AGP) gene is a complex of several additively contributing regulatory sequences. By using deletions and point mutations, a minimal interleukin-1 (IL-1) response element was localized to the region from positions 1 to 36 within the 5'-most AB fragment of the cytokine response element. Two distinct sequence motifs were contained within this element, both of which were required to achieve full IL-1 response in rat and human hepatoma cells. This element showed a minor response to phorbol ester treatment only in human hepatoma cells. Southwestern (DNA-protein) blot analysis of nuclear proteins of rat liver and hepatoma cells revealed the presence of a heat-labile nuclear factor (NF-AB). NF-AB migrated as a basic protein with an apparent molecular mass of 37 kDa and bound specifically to the DNA sequence at positions 10 to 37 of the AB fragment. The NF-AB binding activity was detected neither in the cytoplasmic fraction of rat hepatoma cells nor in nuclear extracts from control or acute-phase rat kidney. The binding activity of NF-AB correlated with the transcriptional activity of the endogenous AGP gene in rat liver and hepatoma cells. Nuclear extract from human HepG2 cells showed a similar binding activity with an apparent molecular mass of 34.5 kDa. The human NF-AB binding activity was detectable only after 13 h of cytokine treatment and was not induced by phorbol ester. Tissue distribution, DNA sequence binding specificity, and kinetics of cytokine induction of NF-AB do not coincide with the characteristics of any other described factors that have been associated with cytokine regulation. Therefore, NF-AB is considered a new candidate involved in IL-1 regulation of the rat AGP gene.
Won
K A
KA
Department of Molecular and Cellular Biology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Baumann
H
H
D000818:Animals; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005796:Genes / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms; D008715:Methionine / Q000378:metabolism; D008970:Molecular Weight; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000378:metabolism*; D009961:Orosomucoid / Q000235:genetics*; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D012045:Regulatory Sequences, Nucleic Acid; D014162:Transfection
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D009687:Nuclear Proteins; D009961:Orosomucoid; D011994:Recombinant Proteins; D003907:Dexamethasone; D008715:Methionine