Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1990 Dec;10(12):6642–6653. doi: 10.1128/mcb.10.12.6642

Molecular cloning of a transcription factor, AGP/EBP, that belongs to members of the C/EBP family.

C J Chang 1, T T Chen 1, H Y Lei 1, D S Chen 1, S C Lee 1
PMCID: PMC362942  PMID: 1701020

Abstract

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.

Full text

PDF
6642

Images in this article

6644Image
on p.6644
6644Image
on p.6644
6645Image
on p.6645
6647Image
on p.6647
6647Image
on p.6647
6649Image
on p.6649
6649Image
on p.6649
6650Image
on p.6650
6651Image
on p.6651

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Agre P., Johnson P. F., McKnight S. L. Cognate DNA binding specificity retained after leucine zipper exchange between GCN4 and C/EBP. Science. 1989 Nov 17;246(4932):922–926. doi: 10.1126/science.2530632. [DOI] [PubMed] [Google Scholar]
  2. Akira S., Isshiki H., Sugita T., Tanabe O., Kinoshita S., Nishio Y., Nakajima T., Hirano T., Kishimoto T. A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J. 1990 Jun;9(6):1897–1906. doi: 10.1002/j.1460-2075.1990.tb08316.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baumann H., Firestone G. L., Burgess T. L., Gross K. W., Yamamoto K. R., Held W. A. Dexamethasone regulation of alpha 1-acid glycoprotein and other acute phase reactants in rat liver and hepatoma cells. J Biol Chem. 1983 Jan 10;258(1):563–570. [PubMed] [Google Scholar]
  4. Baumann H., Held W. A., Berger F. G. The acute phase response of mouse liver. Genetic analysis of the major acute phase reactants. J Biol Chem. 1984 Jan 10;259(1):566–573. [PubMed] [Google Scholar]
  5. Baumann H., Held W. A. Biosynthesis and hormone-regulated expression of secretory glycoproteins in rat liver and hepatoma cells. Effect of glucocorticoids and inflammation. J Biol Chem. 1981 Oct 10;256(19):10145–10155. [PubMed] [Google Scholar]
  6. Baumann H., Hill R. E., Sauder D. N., Jahreis G. P. Regulation of major acute-phase plasma proteins by hepatocyte-stimulating factors of human squamous carcinoma cells. J Cell Biol. 1986 Feb;102(2):370–383. doi: 10.1083/jcb.102.2.370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Baumann H., Maquat L. E. Localization of DNA sequences involved in dexamethasone-dependent expression of the rat alpha 1-acid glycoprotein gene. Mol Cell Biol. 1986 Jul;6(7):2551–2561. doi: 10.1128/mcb.6.7.2551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Birkenmeier E. H., Gwynn B., Howard S., Jerry J., Gordon J. I., Landschulz W. H., McKnight S. L. Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. Genes Dev. 1989 Aug;3(8):1146–1156. doi: 10.1101/gad.3.8.1146. [DOI] [PubMed] [Google Scholar]
  9. Costa R. H., Grayson D. R., Xanthopoulos K. G., Darnell J. E., Jr A liver-specific DNA-binding protein recognizes multiple nucleotide sites in regulatory regions of transthyretin, alpha 1-antitrypsin, albumin, and simian virus 40 genes. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3840–3844. doi: 10.1073/pnas.85.11.3840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Courtois G., Morgan J. G., Campbell L. A., Fourel G., Crabtree G. R. Interaction of a liver-specific nuclear factor with the fibrinogen and alpha 1-antitrypsin promoters. Science. 1987 Oct 30;238(4827):688–692. doi: 10.1126/science.3499668. [DOI] [PubMed] [Google Scholar]
  11. Curran T., Peters G., Van Beveren C., Teich N. M., Verma I. M. FBJ murine osteosarcoma virus: identification and molecular cloning of biologically active proviral DNA. J Virol. 1982 Nov;44(2):674–682. doi: 10.1128/jvi.44.2.674-682.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Darlington G. J., Wilson D. R., Lachman L. B. Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro. J Cell Biol. 1986 Sep;103(3):787–793. doi: 10.1083/jcb.103.3.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  14. Galas D. J., Schmitz A. DNAse footprinting: a simple method for the detection of protein-DNA binding specificity. Nucleic Acids Res. 1978 Sep;5(9):3157–3170. doi: 10.1093/nar/5.9.3157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gauldie J., Richards C., Harnish D., Lansdorp P., Baumann H. Interferon beta 2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7251–7255. doi: 10.1073/pnas.84.20.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Geiger T., Andus T., Klapproth J., Northoff H., Heinrich P. C. Induction of alpha 1-acid glycoprotein by recombinant human interleukin-1 in rat hepatoma cells. J Biol Chem. 1988 May 25;263(15):7141–7146. [PubMed] [Google Scholar]
  17. Grayson D. R., Costa R. H., Xanthopoulos K. G., Darnell J. E. One factor recognizes the liver-specific enhancers in alpha 1-antitrypsin and transthyretin genes. Science. 1988 Feb 12;239(4841 Pt 1):786–788. doi: 10.1126/science.3257586. [DOI] [PubMed] [Google Scholar]
  18. Hai T. W., Liu F., Coukos W. J., Green M. R. Transcription factor ATF cDNA clones: an extensive family of leucine zipper proteins able to selectively form DNA-binding heterodimers. Genes Dev. 1989 Dec;3(12B):2083–2090. doi: 10.1101/gad.3.12b.2083. [DOI] [PubMed] [Google Scholar]
  19. Johnson P. F., Landschulz W. H., Graves B. J., McKnight S. L. Identification of a rat liver nuclear protein that binds to the enhancer core element of three animal viruses. Genes Dev. 1987 Apr;1(2):133–146. doi: 10.1101/gad.1.2.133. [DOI] [PubMed] [Google Scholar]
  20. Karin M., Andersen R. D., Slater E., Smith K., Herschman H. R. Metallothionein mRNA induction in HeLa cells in response to zinc or dexamethasone is a primary induction response. Nature. 1980 Jul 17;286(5770):295–297. doi: 10.1038/286295a0. [DOI] [PubMed] [Google Scholar]
  21. Klein E. S., DiLorenzo D., Posseckert G., Beato M., Ringold G. M. Sequences downstream of the glucocorticoid regulatory element mediate cycloheximide inhibition of steroid induced expression from the rat alpha 1-acid glycoprotein promoter: evidence for a labile transcription factor. Mol Endocrinol. 1988 Dec;2(12):1343–1351. doi: 10.1210/mend-2-12-1343. [DOI] [PubMed] [Google Scholar]
  22. Klein E. S., Reinke R., Feigelson P., Ringold G. M. Glucocorticoid-regulated expression from the 5'-flanking region of the rat alpha 1-acid glycoprotein gene. Requirement for ongoing protein synthesis. J Biol Chem. 1987 Jan 15;262(2):520–523. [PubMed] [Google Scholar]
  23. Kulkarni A. B., Reinke R., Feigelson P. Acute phase mediators and glucocorticoids elevate alpha 1-acid glycoprotein gene transcription. J Biol Chem. 1985 Dec 15;260(29):15386–15389. [PubMed] [Google Scholar]
  24. Landschulz W. H., Johnson P. F., Adashi E. Y., Graves B. J., McKnight S. L. Isolation of a recombinant copy of the gene encoding C/EBP. Genes Dev. 1988 Jul;2(7):786–800. doi: 10.1101/gad.2.7.786. [DOI] [PubMed] [Google Scholar]
  25. Landschulz W. H., Johnson P. F., McKnight S. L. The DNA binding domain of the rat liver nuclear protein C/EBP is bipartite. Science. 1989 Mar 31;243(4899):1681–1688. doi: 10.1126/science.2494700. [DOI] [PubMed] [Google Scholar]
  26. Lee S. C., Chang C. J., Lee Y. M., Lei H. Y., Lai M. Y., Chen D. S. Molecular cloning of cDNAs corresponding to two genes of alpha 1-acid glycoprotein and characterization of two alleles of AGP-1 in the mouse. DNA. 1989 May;8(4):245–251. doi: 10.1089/dna.1.1989.8.245. [DOI] [PubMed] [Google Scholar]
  27. Maire P., Wuarin J., Schibler U. The role of cis-acting promoter elements in tissue-specific albumin gene expression. Science. 1989 Apr 21;244(4902):343–346. doi: 10.1126/science.2711183. [DOI] [PubMed] [Google Scholar]
  28. Miskimins W. K., Roberts M. P., McClelland A., Ruddle F. H. Use of a protein-blotting procedure and a specific DNA probe to identify nuclear proteins that recognize the promoter region of the transferrin receptor gene. Proc Natl Acad Sci U S A. 1985 Oct;82(20):6741–6744. doi: 10.1073/pnas.82.20.6741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  30. Mortensen R. F., Shapiro J., Lin B. F., Douches S., Neta R. Interaction of recombinant IL-1 and recombinant tumor necrosis factor in the induction of mouse acute phase proteins. J Immunol. 1988 Apr 1;140(7):2260–2266. [PubMed] [Google Scholar]
  31. Mueller C. R., Maire P., Schibler U. DBP, a liver-enriched transcriptional activator, is expressed late in ontogeny and its tissue specificity is determined posttranscriptionally. Cell. 1990 Apr 20;61(2):279–291. doi: 10.1016/0092-8674(90)90808-r. [DOI] [PubMed] [Google Scholar]
  32. Peterkofsky B., Tomkins G. M. Evidence for the steroid-induced accumulation of tyrosine-aminotransferase messenger RNA in the absence of protein synthesis. Proc Natl Acad Sci U S A. 1968 May;60(1):222–228. doi: 10.1073/pnas.60.1.222. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Prowse K. R., Baumann H. Hepatocyte-stimulating factor, beta 2 interferon, and interleukin-1 enhance expression of the rat alpha 1-acid glycoprotein gene via a distal upstream regulatory region. Mol Cell Biol. 1988 Jan;8(1):42–51. doi: 10.1128/mcb.8.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ptashne M. How eukaryotic transcriptional activators work. Nature. 1988 Oct 20;335(6192):683–689. doi: 10.1038/335683a0. [DOI] [PubMed] [Google Scholar]
  35. Ramadori G., Sipe J. D., Dinarello C. A., Mizel S. B., Colten H. R. Pretranslational modulation of acute phase hepatic protein synthesis by murine recombinant interleukin 1 (IL-1) and purified human IL-1. J Exp Med. 1985 Sep 1;162(3):930–942. doi: 10.1084/jem.162.3.930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Ricca G. A., Hamilton R. W., McLean J. W., Conn A., Kalinyak J. E., Taylor J. M. Rat alpha 1-acid glycoprotein mRNA. Cloning of double-stranded cDNA and kinetics of induction of mRNA levels following acute inflammation. J Biol Chem. 1981 Oct 25;256(20):10362–10368. [PubMed] [Google Scholar]
  37. Ringold G. M., Yamamoto K. R., Tomkins G. M., Bishop M., Varmus H. E. Dexamethasone-mediated induction of mouse mammary tumor virus RNA: a system for studying glucocorticoid action. Cell. 1975 Nov;6(3):299–305. doi: 10.1016/0092-8674(75)90181-6. [DOI] [PubMed] [Google Scholar]
  38. Singh H., LeBowitz J. H., Baldwin A. S., Jr, Sharp P. A. Molecular cloning of an enhancer binding protein: isolation by screening of an expression library with a recognition site DNA. Cell. 1988 Feb 12;52(3):415–423. doi: 10.1016/s0092-8674(88)80034-5. [DOI] [PubMed] [Google Scholar]
  39. Vannice J. L., Ringold G. M., McLean J. W., Taylor J. M. Induction of the acute-phase reactant, alpha 1-acid glycoprotein, by glucocorticoids in rat hepatoma cells. DNA. 1983;2(3):205–212. doi: 10.1089/dna.1983.2.205. [DOI] [PubMed] [Google Scholar]
  40. Vinson C. R., LaMarco K. L., Johnson P. F., Landschulz W. H., McKnight S. L. In situ detection of sequence-specific DNA binding activity specified by a recombinant bacteriophage. Genes Dev. 1988 Jul;2(7):801–806. doi: 10.1101/gad.2.7.801. [DOI] [PubMed] [Google Scholar]
  41. Vinson C. R., Sigler P. B., McKnight S. L. Scissors-grip model for DNA recognition by a family of leucine zipper proteins. Science. 1989 Nov 17;246(4932):911–916. doi: 10.1126/science.2683088. [DOI] [PubMed] [Google Scholar]
  42. Xanthopoulos K. G., Mirkovitch J., Decker T., Kuo C. F., Darnell J. E., Jr Cell-specific transcriptional control of the mouse DNA-binding protein mC/EBP. Proc Natl Acad Sci U S A. 1989 Jun;86(11):4117–4121. doi: 10.1073/pnas.86.11.4117. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES