A C/EBP-like transcription factor, AGP/EBP, that binds to three distinct motifs in the 5'-flanking region of al-acid glycoprotein gene (AGP) has been identified. Here we report the cloning and properties of cDNA corresponding to mouse AGP/EBP. AGP/EBP and C/EBP share 87% amino acid sequence homology in the "leucine zipper" and its associated DNA-binding domains, while their sequences outside these domains and the sizes of their mRNAs are different. Unlike the limited expression of C/EBP in tissues and cells, AGP/EBP appears to be ubiquitously expressed in tissues like lung, spleen, kidney, heart, testis, and liver and cell lines like p388D1, 129P (hepatoma cell line of C3H/HeJ), FO (mouse myeloma), and L929. Antibody against cloned and expressed AGP/EBP which was raised in rabbits could recognize AGP/EBP from nuclear extract of a number of cells and tissues. On the basis of our findings about the structural relationship and the similarity of motif recognition, we propose that a family of C/EBP-like transcription factors exists. a,-Acid glycoprotein (AGP) is a liver-derived plasma glycoprotein which increases severalfold during acute-phase reaction (3-5, 37). AGP is transcriptionally regulated in rat, mouse, and human hepatocytes by interleukin-1 (IL-1) (31,34,36), hepatocyte-stimulating factor (beta interferon subtype 2 and IL-6) (6,13,16,24), and glucocorticoids (3,4,7,22,23,40). In the rat AGP gene, the hormonal stimulation by IL-1 and IL-6 is mediated by the distal regulatory element located at -5300 to -5150 (34), and the glucocorticoidresponsive element has been limited to positions -120 to -42 (7). The corresponding enhancer elements in the human and mouse AGP genes have not yet been defined. Unlike many glucocorticoid-responsive genes, such as those encoding the mouse mammary tumor virus (38, 40), human metallothionein (21), and tyrosine aminotransferase (33), the induction of AGP RNA by glucocorticoids is diminished in cells treated with protein synthesis inhibitor (e.g., cycloheximide) (3,22,23). It has been demonstrated that the rat AGP 5'-flanking region contains a DNA sequence (-121 to -107), exhibiting a high degree of homology to the glucocorticoid-responsive element consensus sequence 5'-GGTACAN3TGTTCT-3', which serves to specifically bind purified rat glucocorticoid receptor in vitro (22). A 15-bp oligonucleotide representing the rat AGP glucocorticoidresponsive element (5'-GGAACATTTTGTGCA-3') confers glucocorticoid responsiveness on a heterologous promoter; such regulation is not diminished by concurrent inhibition of protein synthesis. However, inclusion of the AGP sequences immediately downstream of the AGP glucocorticoid-responsive element (-106 to -42) renders the hormonal induction sensitive to inhibition of protein synthesis (22). DNase I footprinting with nuclear extracts prepared from HTC hepatoma cells indicates the presence of DNA-protein interactions spanning the region from -110 to -68 of the rat AGP gene (22).Three functional AGP genes (Agp-1, Agp-2, and Agp-3) have been isolated f...

A C/EBP-like transcription factor, AGP/EBP, that binds to three distinct motifs in the 5'-flanking region of alpha 1-acid glycoprotein gene (AGP) has been identified. Here we report the cloning and properties of cDNA corresponding to mouse AGP/EBP. AGP/EBP and C/EBP share 87% amino acid sequence homology in the "leucine zipper" and its associated DNA-binding domains, while their sequences outside these domains and the sizes of their mRNAs are different. Unlike the limited expression of C/EBP in tissues and cells, AGP/EBP appears to be ubiquitously expressed in tissues like lung, spleen, kidney, heart, testis, and liver and cell lines like p388D1, 129P (hepatoma cell line of C3H/HeJ), FO (mouse myeloma), and L929. Antibody against cloned and expressed AGP/EBP which was raised in rabbits could recognize AGP/EBP from nuclear extract of a number of cells and tissues. On the basis of our findings about the structural relationship and the similarity of motif recognition, we propose that a family of C/EBP-like transcription factors exists.