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. 1997 Jan;17(1):61–68. doi: 10.1128/mcb.17.1.61

Suppression of grp78 core promoter element-mediated stress induction by the dbpA and dbpB (YB-1) cold shock domain proteins.

W W Li 1, Y Hsiung 1, V Wong 1, K Galvin 1, Y Zhou 1, Y Shi 1, A S Lee 1
PMCID: PMC231730  PMID: 8972186

Abstract

The highly conserved grp78 core promoter element plays an important role in the induction of grp78 under diverse stress signals. Previous studies have established a functional region in the 3' half of the core (stress-inducible change region [SICR]) which exhibits stress-inducible changes in stressed nuclei. The human transcription factor YY1 is shown to bind the SICR and transactivate the core element under stress conditions. Here we report that expression library screening with the core element has identified two new core binding proteins, YB-1 and dbpA. Both proteins belong to the Y-box family of proteins characterized by an evolutionarily conserved DNA binding motif, the cold shock domain (CSD). In contrast to YY1, which binds only double-stranded SICR, the Y-box/CSD proteins much prefer the lower strand of the SICR. The Y-box proteins can repress the inducibility of the grp78 core element mediated by treatment of cells with A23187, thapsigargin, and tunicamycin. In gel shift assays, YY1 binding to the core element is inhibited by either YB-1 or dbpA. A yeast interaction trap screen using LexA-YY1 as a bait and a HeLa cell cDNA-acid patch fusion library identified YB-1 as a YY1-interacting protein. In cotransfection experiments, the Y-box proteins antagonize the YY1-mediated enhancement of transcription directed by the grp78 core in stressed cells. Thus, the CSD proteins may be part of the stress signal transduction mechanism in the mammalian system.

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Selected References

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  1. Altschul S. F., Gish W., Miller W., Myers E. W., Lipman D. J. Basic local alignment search tool. J Mol Biol. 1990 Oct 5;215(3):403–410. doi: 10.1016/S0022-2836(05)80360-2. [DOI] [PubMed] [Google Scholar]
  2. Beckmann H., Su L. K., Kadesch T. TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif. Genes Dev. 1990 Feb;4(2):167–179. doi: 10.1101/gad.4.2.167. [DOI] [PubMed] [Google Scholar]
  3. Cao X., Zhou Y., Lee A. S. Requirement of tyrosine- and serine/threonine kinases in the transcriptional activation of the mammalian grp78/BiP promoter by thapsigargin. J Biol Chem. 1995 Jan 6;270(1):494–502. doi: 10.1074/jbc.270.1.494. [DOI] [PubMed] [Google Scholar]
  4. Chen N. N., Chang C. F., Gallia G. L., Kerr D. A., Johnson E. M., Krachmarov C. P., Barr S. M., Frisque R. J., Bollag B., Khalili K. Cooperative action of cellular proteins YB-1 and Pur alpha with the tumor antigen of the human JC polyomavirus determines their interaction with the viral lytic control element. Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1087–1091. doi: 10.1073/pnas.92.4.1087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Didier D. K., Schiffenbauer J., Woulfe S. L., Zacheis M., Schwartz B. D. Characterization of the cDNA encoding a protein binding to the major histocompatibility complex class II Y box. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7322–7326. doi: 10.1073/pnas.85.19.7322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Drummond I. A., Lee A. S., Resendez E., Jr, Steinhardt R. A. Depletion of intracellular calcium stores by calcium ionophore A23187 induces the genes for glucose-regulated proteins in hamster fibroblasts. J Biol Chem. 1987 Sep 15;262(26):12801–12805. [PubMed] [Google Scholar]
  7. Gai X. X., Lipson K. E., Prystowsky M. B. Unusual DNA binding characteristics of an in vitro translation product of the CCAAT binding protein mYB-1. Nucleic Acids Res. 1992 Feb 11;20(3):601–606. doi: 10.1093/nar/20.3.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hammond C., Helenius A. Quality control in the secretory pathway: retention of a misfolded viral membrane glycoprotein involves cycling between the ER, intermediate compartment, and Golgi apparatus. J Cell Biol. 1994 Jul;126(1):41–52. doi: 10.1083/jcb.126.1.41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hasegawa S. L., Doetsch P. W., Hamilton K. K., Martin A. M., Okenquist S. A., Lenz J., Boss J. M. DNA binding properties of YB-1 and dbpA: binding to double-stranded, single-stranded, and abasic site containing DNAs. Nucleic Acids Res. 1991 Sep 25;19(18):4915–4920. doi: 10.1093/nar/19.18.4915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Ito K., Tsutsumi K., Kuzumaki T., Gomez P. F., Otsu K., Ishikawa K. A novel growth-inducible gene that encodes a protein with a conserved cold-shock domain. Nucleic Acids Res. 1994 Jun 11;22(11):2036–2041. doi: 10.1093/nar/22.11.2036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Johnstone R. W., See R. H., Sells S. F., Wang J., Muthukkumar S., Englert C., Haber D. A., Licht J. D., Sugrue S. P., Roberts T. A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1. Mol Cell Biol. 1996 Dec;16(12):6945–6956. doi: 10.1128/mcb.16.12.6945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kashanchi F., Duvall J. F., Dittmer J., Mireskandari A., Reid R. L., Gitlin S. D., Brady J. N. Involvement of transcription factor YB-1 in human T-cell lymphotropic virus type I basal gene expression. J Virol. 1994 Jan;68(1):561–565. doi: 10.1128/jvi.68.1.561-565.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kerr D., Chang C. F., Chen N., Gallia G., Raj G., Schwartz B., Khalili K. Transcription of a human neurotropic virus promoter in glial cells: effect of YB-1 on expression of the JC virus late gene. J Virol. 1994 Nov;68(11):7637–7643. doi: 10.1128/jvi.68.11.7637-7643.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kudo S., Mattei M. G., Fukuda M. Characterization of the gene for dbpA, a family member of the nucleic-acid-binding proteins containing a cold-shock domain. Eur J Biochem. 1995 Jul 1;231(1):72–82. doi: 10.1111/j.1432-1033.1995.tb20672.x. [DOI] [PubMed] [Google Scholar]
  15. Lee A. S. Mammalian stress response: induction of the glucose-regulated protein family. Curr Opin Cell Biol. 1992 Apr;4(2):267–273. doi: 10.1016/0955-0674(92)90042-b. [DOI] [PubMed] [Google Scholar]
  16. Lee J. S., Galvin K. M., Shi Y. Evidence for physical interaction between the zinc-finger transcription factors YY1 and Sp1. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6145–6149. doi: 10.1073/pnas.90.13.6145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Li W. W., Alexandre S., Cao X., Lee A. S. Transactivation of the grp78 promoter by Ca2+ depletion. A comparative analysis with A23187 and the endoplasmic reticulum Ca(2+)-ATPase inhibitor thapsigargin. J Biol Chem. 1993 Jun 5;268(16):12003–12009. [PubMed] [Google Scholar]
  18. Li W. W., Hsiung Y., Zhou Y., Roy B., Lee A. S. Induction of the mammalian GRP78/BiP gene by Ca2+ depletion and formation of aberrant proteins: activation of the conserved stress-inducible grp core promoter element by the human nuclear factor YY1. Mol Cell Biol. 1997 Jan;17(1):54–60. doi: 10.1128/mcb.17.1.54. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Li W. W., Sistonen L., Morimoto R. I., Lee A. S. Stress induction of the mammalian GRP78/BiP protein gene: in vivo genomic footprinting and identification of p70CORE from human nuclear extract as a DNA-binding component specific to the stress regulatory element. Mol Cell Biol. 1994 Aug;14(8):5533–5546. doi: 10.1128/mcb.14.8.5533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lin A. Y., Chang S. C., Lee A. S. A calcium ionophore-inducible cellular promoter is highly active and has enhancerlike properties. Mol Cell Biol. 1986 Apr;6(4):1235–1243. doi: 10.1128/mcb.6.4.1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Liu E. S., Lee A. S. Common sets of nuclear factors binding to the conserved promoter sequence motif of two coordinately regulated ER protein genes, GRP78 and GRP94. Nucleic Acids Res. 1991 Oct 11;19(19):5425–5431. doi: 10.1093/nar/19.19.5425. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lloberas J., Maki R. A., Celada A. Repression of major histocompatibility complex I-A beta gene expression by dbpA and dbpB (mYB-1) proteins. Mol Cell Biol. 1995 Sep;15(9):5092–5099. doi: 10.1128/mcb.15.9.5092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lum L. S., Sultzman L. A., Kaufman R. J., Linzer D. I., Wu B. J. A cloned human CCAAT-box-binding factor stimulates transcription from the human hsp70 promoter. Mol Cell Biol. 1990 Dec;10(12):6709–6717. doi: 10.1128/mcb.10.12.6709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. MacDonald G. H., Itoh-Lindstrom Y., Ting J. P. The transcriptional regulatory protein, YB-1, promotes single-stranded regions in the DRA promoter. J Biol Chem. 1995 Feb 24;270(8):3527–3533. doi: 10.1074/jbc.270.8.3527. [DOI] [PubMed] [Google Scholar]
  25. Melnick J., Dul J. L., Argon Y. Sequential interaction of the chaperones BiP and GRP94 with immunoglobulin chains in the endoplasmic reticulum. Nature. 1994 Aug 4;370(6488):373–375. doi: 10.1038/370373a0. [DOI] [PubMed] [Google Scholar]
  26. Mori K., Sant A., Kohno K., Normington K., Gething M. J., Sambrook J. F. A 22 bp cis-acting element is necessary and sufficient for the induction of the yeast KAR2 (BiP) gene by unfolded proteins. EMBO J. 1992 Jul;11(7):2583–2593. doi: 10.1002/j.1460-2075.1992.tb05323.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nakaki T., Deans R. J., Lee A. S. Enhanced transcription of the 78,000-dalton glucose-regulated protein (GRP78) gene and association of GRP78 with immunoglobulin light chains in a nonsecreting B-cell myeloma line (NS-1). Mol Cell Biol. 1989 May;9(5):2233–2238. doi: 10.1128/mcb.9.5.2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ozer J., Faber M., Chalkley R., Sealy L. Isolation and characterization of a cDNA clone for the CCAAT transcription factor EFIA reveals a novel structural motif. J Biol Chem. 1990 Dec 25;265(36):22143–22152. [PubMed] [Google Scholar]
  29. Roy B., Lee A. S. Transduction of calcium stress through interaction of the human transcription factor CBF with the proximal CCAAT regulatory element of the grp78/BiP promoter. Mol Cell Biol. 1995 Apr;15(4):2263–2274. doi: 10.1128/mcb.15.4.2263. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Roy B., Li W. W., Lee A. S. Calcium-sensitive transcriptional activation of the proximal CCAAT regulatory element of the grp78/BiP promoter by the human nuclear factor CBF/NF-Y. J Biol Chem. 1996 Nov 15;271(46):28995–29002. doi: 10.1074/jbc.271.46.28995. [DOI] [PubMed] [Google Scholar]
  31. Sakura H., Maekawa T., Imamoto F., Yasuda K., Ishii S. Two human genes isolated by a novel method encode DNA-binding proteins containing a common region of homology. Gene. 1988 Dec 20;73(2):499–507. doi: 10.1016/0378-1119(88)90514-8. [DOI] [PubMed] [Google Scholar]
  32. Schindelin H., Jiang W., Inouye M., Heinemann U. Crystal structure of CspA, the major cold shock protein of Escherichia coli. Proc Natl Acad Sci U S A. 1994 May 24;91(11):5119–5123. doi: 10.1073/pnas.91.11.5119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ting J. P., Painter A., Zeleznik-Le N. J., MacDonald G., Moore T. M., Brown A., Schwartz B. D. YB-1 DNA-binding protein represses interferon gamma activation of class II major histocompatibility complex genes. J Exp Med. 1994 May 1;179(5):1605–1611. doi: 10.1084/jem.179.5.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. Wistow G. Cold shock and DNA binding. Nature. 1990 Apr 26;344(6269):823–824. doi: 10.1038/344823c0. [DOI] [PubMed] [Google Scholar]
  36. Wolffe A. P. Structural and functional properties of the evolutionarily ancient Y-box family of nucleic acid binding proteins. Bioessays. 1994 Apr;16(4):245–251. doi: 10.1002/bies.950160407. [DOI] [PubMed] [Google Scholar]
  37. Wooden S. K., Li L. J., Navarro D., Qadri I., Pereira L., Lee A. S. Transactivation of the grp78 promoter by malfolded proteins, glycosylation block, and calcium ionophore is mediated through a proximal region containing a CCAAT motif which interacts with CTF/NF-I. Mol Cell Biol. 1991 Nov;11(11):5612–5623. doi: 10.1128/mcb.11.11.5612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Zervos A. S., Gyuris J., Brent R. Mxi1, a protein that specifically interacts with Max to bind Myc-Max recognition sites. Cell. 1993 Jan 29;72(2):223–232. doi: 10.1016/0092-8674(93)90662-a. [DOI] [PubMed] [Google Scholar]
  39. Zou Y., Chien K. R. EFIA/YB-1 is a component of cardiac HF-1A binding activity and positively regulates transcription of the myosin light-chain 2v gene. Mol Cell Biol. 1995 Jun;15(6):2972–2982. doi: 10.1128/mcb.15.6.2972. [DOI] [PMC free article] [PubMed] [Google Scholar]

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