Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1993 May 15;292(Pt 1):41–45. doi: 10.1042/bj2920041

Interaction of transcription factor Sp1 with the promoter of the gene for the multifunctional protein disulphide isomerase polypeptide.

K Tasanen 1, J Oikarinen 1, K I Kivirikko 1, T Pihlajaniemi 1
PMCID: PMC1134266  PMID: 8503862

Abstract

Protein disulphide isomerase (PDI) is a unique polypeptide which resides in the lumen of the endoplasmic reticulum and also functions as the beta-subunit of prolyl 4-hydroxylase, as a cellular thyroid hormone-binding protein, as the smaller subunit of the microsomal triacylglycerol transfer protein complex, as a dehydroascorbate reductase and as a protein that binds various peptides in a specific manner. We have recently demonstrated that the promoter of the PDI gene contains six CCAAT boxes and other elements which are needed for efficient transcription. We now demonstrate that purified human recombinant transcription factor Sp1 interacts with two perfect GGGCGG sequences and three other GC-rich elements of the PDI promoter. Sp1 also appears to participate in the regulation of PDI gene expression, since overexpression of Sp1 stimulated PDI promoter activity in HeLa cells and mutations introduced into each of these Sp1-binding sites separately reduced the promoter strength, although even the largest decrease was only about 50%. These results support our view that expression of the gene for this polypeptide with multiple functions is secured by several regulatory elements, some of which are functionally redundant.

Full text

PDF
43

Images in this article

43Figure 2
on p.43

Selected References

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

  1. Anfinsen C. B., Scheraga H. A. Experimental and theoretical aspects of protein folding. Adv Protein Chem. 1975;29:205–300. doi: 10.1016/s0065-3233(08)60413-1. [DOI] [PubMed] [Google Scholar]
  2. Cheng S. Y., Gong Q. H., Parkison C., Robinson E. A., Appella E., Merlino G. T., Pastan I. The nucleotide sequence of a human cellular thyroid hormone binding protein present in endoplasmic reticulum. J Biol Chem. 1987 Aug 15;262(23):11221–11227. [PubMed] [Google Scholar]
  3. Corneliussen B., Thornell A., Hallberg B., Grundström T. Helix-loop-helix transcriptional activators bind to a sequence in glucocorticoid response elements of retrovirus enhancers. J Virol. 1991 Nov;65(11):6084–6093. doi: 10.1128/jvi.65.11.6084-6093.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Courey A. J., Holtzman D. A., Jackson S. P., Tjian R. Synergistic activation by the glutamine-rich domains of human transcription factor Sp1. Cell. 1989 Dec 1;59(5):827–836. doi: 10.1016/0092-8674(89)90606-5. [DOI] [PubMed] [Google Scholar]
  5. Courey A. J., Tjian R. Analysis of Sp1 in vivo reveals multiple transcriptional domains, including a novel glutamine-rich activation motif. Cell. 1988 Dec 2;55(5):887–898. doi: 10.1016/0092-8674(88)90144-4. [DOI] [PubMed] [Google Scholar]
  6. Edman J. C., Ellis L., Blacher R. W., Roth R. A., Rutter W. J. Sequence of protein disulphide isomerase and implications of its relationship to thioredoxin. Nature. 1985 Sep 19;317(6034):267–270. doi: 10.1038/317267a0. [DOI] [PubMed] [Google Scholar]
  7. Farquhar R., Honey N., Murant S. J., Bossier P., Schultz L., Montgomery D., Ellis R. W., Freedman R. B., Tuite M. F. Protein disulfide isomerase is essential for viability in Saccharomyces cerevisiae. Gene. 1991 Dec 1;108(1):81–89. doi: 10.1016/0378-1119(91)90490-3. [DOI] [PubMed] [Google Scholar]
  8. Freedman R. B., Bulleid N. J., Hawkins H. C., Paver J. L. Role of protein disulphide-isomerase in the expression of native proteins. Biochem Soc Symp. 1989;55:167–192. [PubMed] [Google Scholar]
  9. Freedman R. B. Protein disulfide isomerase: multiple roles in the modification of nascent secretory proteins. Cell. 1989 Jun 30;57(7):1069–1072. doi: 10.1016/0092-8674(89)90043-3. [DOI] [PubMed] [Google Scholar]
  10. Geetha-Habib M., Noiva R., Kaplan H. A., Lennarz W. J. Glycosylation site binding protein, a component of oligosaccharyl transferase, is highly similar to three other 57 kd luminal proteins of the ER. Cell. 1988 Sep 23;54(7):1053–1060. doi: 10.1016/0092-8674(88)90120-1. [DOI] [PubMed] [Google Scholar]
  11. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Helaakoski T., Pajunen L., Kivirikko K. I., Pihlajaniemi T. Increases in mRNA concentrations of the alpha and beta subunits of prolyl 4-hydroxylase accompany increased gene expression of type IV collagen during differentiation of mouse F9 cells. J Biol Chem. 1990 Jul 15;265(20):11413–11416. [PubMed] [Google Scholar]
  13. Kadonaga J. T., Carner K. R., Masiarz F. R., Tjian R. Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain. Cell. 1987 Dec 24;51(6):1079–1090. doi: 10.1016/0092-8674(87)90594-0. [DOI] [PubMed] [Google Scholar]
  14. Kadonaga J. T., Courey A. J., Ladika J., Tjian R. Distinct regions of Sp1 modulate DNA binding and transcriptional activation. Science. 1988 Dec 16;242(4885):1566–1570. doi: 10.1126/science.3059495. [DOI] [PubMed] [Google Scholar]
  15. Kivirikko K. I., Helaakoski T., Tasanen K., Vuori K., Myllylä R., Parkkonen T., Pihlajaniemi T. Molecular biology of prolyl 4-hydroxylase. Ann N Y Acad Sci. 1990;580:132–142. doi: 10.1111/j.1749-6632.1990.tb17925.x. [DOI] [PubMed] [Google Scholar]
  16. Kivirikko K. I., Myllylä R., Pihlajaniemi T. Protein hydroxylation: prolyl 4-hydroxylase, an enzyme with four cosubstrates and a multifunctional subunit. FASEB J. 1989 Mar;3(5):1609–1617. [PubMed] [Google Scholar]
  17. Koivu J., Myllylä R., Helaakoski T., Pihlajaniemi T., Tasanen K., Kivirikko K. I. A single polypeptide acts both as the beta subunit of prolyl 4-hydroxylase and as a protein disulfide-isomerase. J Biol Chem. 1987 May 15;262(14):6447–6449. [PubMed] [Google Scholar]
  18. LaMantia M., Miura T., Tachikawa H., Kaplan H. A., Lennarz W. J., Mizunaga T. Glycosylation site binding protein and protein disulfide isomerase are identical and essential for cell viability in yeast. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4453–4457. doi: 10.1073/pnas.88.10.4453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mastrangelo I. A., Courey A. J., Wall J. S., Jackson S. P., Hough P. V. DNA looping and Sp1 multimer links: a mechanism for transcriptional synergism and enhancement. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5670–5674. doi: 10.1073/pnas.88.13.5670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Myllylä R., Koivu J., Pihlajaniemi T., Kivirikko K. I. Protein disulphide-isomerase activity in various cells synthesizing collagen. Eur J Biochem. 1983 Jul 15;134(1):7–11. doi: 10.1111/j.1432-1033.1983.tb07523.x. [DOI] [PubMed] [Google Scholar]
  21. Noiva R., Kaplan H. A., Lennarz W. J. Glycosylation site-binding protein is not required for N-linked glycoprotein synthesis. Proc Natl Acad Sci U S A. 1991 Mar 1;88(5):1986–1990. doi: 10.1073/pnas.88.5.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pascal E., Tjian R. Different activation domains of Sp1 govern formation of multimers and mediate transcriptional synergism. Genes Dev. 1991 Sep;5(9):1646–1656. doi: 10.1101/gad.5.9.1646. [DOI] [PubMed] [Google Scholar]
  23. Pihlajaniemi T., Helaakoski T., Tasanen K., Myllylä R., Huhtala M. L., Koivu J., Kivirikko K. I. Molecular cloning of the beta-subunit of human prolyl 4-hydroxylase. This subunit and protein disulphide isomerase are products of the same gene. EMBO J. 1987 Mar;6(3):643–649. doi: 10.1002/j.1460-2075.1987.tb04803.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Roth R. A., Koshland M. E. Role of disulfide interchange enzyme in immunoglobulin synthesis. Biochemistry. 1981 Nov 10;20(23):6594–6599. doi: 10.1021/bi00526a012. [DOI] [PubMed] [Google Scholar]
  25. Saffer J. D., Jackson S. P., Annarella M. B. Developmental expression of Sp1 in the mouse. Mol Cell Biol. 1991 Apr;11(4):2189–2199. doi: 10.1128/mcb.11.4.2189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saffer J. D., Jackson S. P., Thurston S. J. SV40 stimulates expression of the transacting factor Sp1 at the mRNA level. Genes Dev. 1990 Apr;4(4):659–666. doi: 10.1101/gad.4.4.659. [DOI] [PubMed] [Google Scholar]
  27. Scherens B., Dubois E., Messenguy F. Determination of the sequence of the yeast YCL313 gene localized on chromosome III. Homology with the protein disulfide isomerase (PDI gene product) of other organisms. Yeast. 1991 Feb;7(2):185–193. doi: 10.1002/yea.320070212. [DOI] [PubMed] [Google Scholar]
  28. Selden R. F., Howie K. B., Rowe M. E., Goodman H. M., Moore D. D. Human growth hormone as a reporter gene in regulation studies employing transient gene expression. Mol Cell Biol. 1986 Sep;6(9):3173–3179. doi: 10.1128/mcb.6.9.3173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Su W., Jackson S., Tjian R., Echols H. DNA looping between sites for transcriptional activation: self-association of DNA-bound Sp1. Genes Dev. 1991 May;5(5):820–826. doi: 10.1101/gad.5.5.820. [DOI] [PubMed] [Google Scholar]
  30. Tachikawa H., Miura T., Katakura Y., Mizunaga T. Molecular structure of a yeast gene, PDI1, encoding protein disulfide isomerase that is essential for cell growth. J Biochem. 1991 Aug;110(2):306–313. doi: 10.1093/oxfordjournals.jbchem.a123576. [DOI] [PubMed] [Google Scholar]
  31. Tasanen K., Oikarinen J., Kivirikko K. I., Pihlajaniemi T. Promoter of the gene for the multifunctional protein disulfide isomerase polypeptide. Functional significance of the six CCAAT boxes and other promoter elements. J Biol Chem. 1992 Jun 5;267(16):11513–11519. [PubMed] [Google Scholar]
  32. Tasanen K., Parkkonen T., Chow L. T., Kivirikko K. I., Pihlajaniemi T. Characterization of the human gene for a polypeptide that acts both as the beta subunit of prolyl 4-hydroxylase and as protein disulfide isomerase. J Biol Chem. 1988 Nov 5;263(31):16218–16224. [PubMed] [Google Scholar]
  33. Wells W. W., Xu D. P., Yang Y. F., Rocque P. A. Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity. J Biol Chem. 1990 Sep 15;265(26):15361–15364. [PubMed] [Google Scholar]
  34. Wetterau J. R., Combs K. A., McLean L. R., Spinner S. N., Aggerbeck L. P. Protein disulfide isomerase appears necessary to maintain the catalytically active structure of the microsomal triglyceride transfer protein. Biochemistry. 1991 Oct 8;30(40):9728–9735. doi: 10.1021/bi00104a023. [DOI] [PubMed] [Google Scholar]
  35. Wetterau J. R., Combs K. A., Spinner S. N., Joiner B. J. Protein disulfide isomerase is a component of the microsomal triglyceride transfer protein complex. J Biol Chem. 1990 Jun 15;265(17):9800–9807. [PubMed] [Google Scholar]
  36. Yamauchi K., Yamamoto T., Hayashi H., Koya S., Takikawa H., Toyoshima K., Horiuchi R. Sequence of membrane-associated thyroid hormone binding protein from bovine liver: its identity with protein disulphide isomerase. Biochem Biophys Res Commun. 1987 Aug 14;146(3):1485–1492. doi: 10.1016/0006-291x(87)90817-5. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES