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. 1996 Sep 15;24(18):3607–3613. doi: 10.1093/nar/24.18.3607

Protein-protein interaction between the transcriptional repressor E4BP4 and the TBP-binding protein Dr1.

I G Cowell 1, H C Hurst 1
PMCID: PMC146135  PMID: 8836190

Abstract

We have previously mapped a repression domain from the active transcriptional repressor E4BP4 to a 65 amino acid segment near the C-terminus of the polypeptide. Here we show that the E4BP4 repression domain interacts specifically with the TBP binding repressor protein Dr1. Mutants that affect the ability of E4BP4 to bring about transcriptional repression are also deficient in their binding of Dr1. The results are discussed in the light of evidence for squelching of a 'global' repressor by a DNA binding defective E4BP4 mutant.

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Selected References

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  1. Baniahmad A., Köhne A. C., Renkawitz R. A transferable silencing domain is present in the thyroid hormone receptor, in the v-erbA oncogene product and in the retinoic acid receptor. EMBO J. 1992 Mar;11(3):1015–1023. doi: 10.1002/j.1460-2075.1992.tb05140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bjornsti M. A., Benedetti P., Viglianti G. A., Wang J. C. Expression of human DNA topoisomerase I in yeast cells lacking yeast DNA topoisomerase I: restoration of sensitivity of the cells to the antitumor drug camptothecin. Cancer Res. 1989 Nov 15;49(22):6318–6323. [PubMed] [Google Scholar]
  3. Burch J. B., Davis D. L. Alternative promoter usage and splicing options result in the differential expression of mRNAs encoding four isoforms of chicken VBP, a member of the PAR subfamily of bZIP transcription factors. Nucleic Acids Res. 1994 Nov 11;22(22):4733–4741. doi: 10.1093/nar/22.22.4733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chen B. P., Liang G., Whelan J., Hai T. ATF3 and ATF3 delta Zip. Transcriptional repression versus activation by alternatively spliced isoforms. J Biol Chem. 1994 Jun 3;269(22):15819–15826. [PubMed] [Google Scholar]
  5. Cowell I. G., Dixon K. H., Pemble S. E., Ketterer B., Taylor J. B. The structure of the human glutathione S-transferase pi gene. Biochem J. 1988 Oct 1;255(1):79–83. doi: 10.1042/bj2550079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cowell I. G., Hurst H. C. Transcriptional repression by the human bZIP factor E4BP4: definition of a minimal repression domain. Nucleic Acids Res. 1994 Jan 11;22(1):59–65. doi: 10.1093/nar/22.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cowell I. G. Repression versus activation in the control of gene transcription. Trends Biochem Sci. 1994 Jan;19(1):38–42. doi: 10.1016/0968-0004(94)90172-4. [DOI] [PubMed] [Google Scholar]
  8. Cowell I. G., Skinner A., Hurst H. C. Transcriptional repression by a novel member of the bZIP family of transcription factors. Mol Cell Biol. 1992 Jul;12(7):3070–3077. doi: 10.1128/mcb.12.7.3070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dixon K. H., Cowell I. G., Xia C. L., Pemble S. E., Ketterer B., Taylor J. B. Control of expression of the human glutathione S-transferase pi gene differs from its rat orthologue. Biochem Biophys Res Commun. 1989 Sep 15;163(2):815–822. doi: 10.1016/0006-291x(89)92295-x. [DOI] [PubMed] [Google Scholar]
  10. Fields S., Song O. A novel genetic system to detect protein-protein interactions. Nature. 1989 Jul 20;340(6230):245–246. doi: 10.1038/340245a0. [DOI] [PubMed] [Google Scholar]
  11. Fondell J. D., Brunel F., Hisatake K., Roeder R. G. Unliganded thyroid hormone receptor alpha can target TATA-binding protein for transcriptional repression. Mol Cell Biol. 1996 Jan;16(1):281–287. doi: 10.1128/mcb.16.1.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fondell J. D., Roy A. L., Roeder R. G. Unliganded thyroid hormone receptor inhibits formation of a functional preinitiation complex: implications for active repression. Genes Dev. 1993 Jul;7(7B):1400–1410. doi: 10.1101/gad.7.7b.1400. [DOI] [PubMed] [Google Scholar]
  13. Fonjallaz P., Ossipow V., Wanner G., Schibler U. The two PAR leucine zipper proteins, TEF and DBP, display similar circadian and tissue-specific expression, but have different target promoter preferences. EMBO J. 1996 Jan 15;15(2):351–362. [PMC free article] [PubMed] [Google Scholar]
  14. Gill G., Ptashne M. Negative effect of the transcriptional activator GAL4. Nature. 1988 Aug 25;334(6184):721–724. doi: 10.1038/334721a0. [DOI] [PubMed] [Google Scholar]
  15. Gray S., Szymanski P., Levine M. Short-range repression permits multiple enhancers to function autonomously within a complex promoter. Genes Dev. 1994 Aug 1;8(15):1829–1838. doi: 10.1101/gad.8.15.1829. [DOI] [PubMed] [Google Scholar]
  16. Han K., Manley J. L. Functional domains of the Drosophila Engrailed protein. EMBO J. 1993 Jul;12(7):2723–2733. doi: 10.1002/j.1460-2075.1993.tb05934.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Han K., Manley J. L. Transcriptional repression by the Drosophila even-skipped protein: definition of a minimal repression domain. Genes Dev. 1993 Mar;7(3):491–503. doi: 10.1101/gad.7.3.491. [DOI] [PubMed] [Google Scholar]
  18. Hörlein A. J., När A. M., Heinzel T., Torchia J., Gloss B., Kurokawa R., Ryan A., Kamei Y., Söderström M., Glass C. K. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature. 1995 Oct 5;377(6548):397–404. doi: 10.1038/377397a0. [DOI] [PubMed] [Google Scholar]
  19. Inostroza J. A., Mermelstein F. H., Ha I., Lane W. S., Reinberg D. Dr1, a TATA-binding protein-associated phosphoprotein and inhibitor of class II gene transcription. Cell. 1992 Aug 7;70(3):477–489. doi: 10.1016/0092-8674(92)90172-9. [DOI] [PubMed] [Google Scholar]
  20. Kraus V. B., Inostroza J. A., Yeung K., Reinberg D., Nevins J. R. Interaction of the Dr1 inhibitory factor with the TATA binding protein is disrupted by adenovirus E1A. Proc Natl Acad Sci U S A. 1994 Jul 5;91(14):6279–6282. doi: 10.1073/pnas.91.14.6279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kretzschmar M., Meisterernst M., Roeder R. G. Identification of human DNA topoisomerase I as a cofactor for activator-dependent transcription by RNA polymerase II. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11508–11512. doi: 10.1073/pnas.90.24.11508. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lee W. S., Kao C. C., Bryant G. O., Liu X., Berk A. J. Adenovirus E1A activation domain binds the basic repeat in the TATA box transcription factor. Cell. 1991 Oct 18;67(2):365–376. doi: 10.1016/0092-8674(91)90188-5. [DOI] [PubMed] [Google Scholar]
  23. Lillie J. W., Green M. R. Transcription activation by the adenovirus E1a protein. Nature. 1989 Mar 2;338(6210):39–44. doi: 10.1038/338039a0. [DOI] [PubMed] [Google Scholar]
  24. Madden S. L., Cook D. M., Morris J. F., Gashler A., Sukhatme V. P., Rauscher F. J., 3rd Transcriptional repression mediated by the WT1 Wilms tumor gene product. Science. 1991 Sep 27;253(5027):1550–1553. doi: 10.1126/science.1654597. [DOI] [PubMed] [Google Scholar]
  25. Meisterernst M., Roeder R. G. Family of proteins that interact with TFIID and regulate promoter activity. Cell. 1991 Nov 1;67(3):557–567. doi: 10.1016/0092-8674(91)90530-c. [DOI] [PubMed] [Google Scholar]
  26. Meisterernst M., Roy A. L., Lieu H. M., Roeder R. G. Activation of class II gene transcription by regulatory factors is potentiated by a novel activity. Cell. 1991 Sep 6;66(5):981–993. doi: 10.1016/0092-8674(91)90443-3. [DOI] [PubMed] [Google Scholar]
  27. Merino A., Madden K. R., Lane W. S., Champoux J. J., Reinberg D. DNA topoisomerase I is involved in both repression and activation of transcription. Nature. 1993 Sep 16;365(6443):227–232. doi: 10.1038/365227a0. [DOI] [PubMed] [Google Scholar]
  28. Mermelstein F., Yeung K., Cao J., Inostroza J. A., Erdjument-Bromage H., Eagelson K., Landsman D., Levitt P., Tempst P., Reinberg D. Requirement of a corepressor for Dr1-mediated repression of transcription. Genes Dev. 1996 Apr 15;10(8):1033–1048. doi: 10.1101/gad.10.8.1033. [DOI] [PubMed] [Google Scholar]
  29. Nikolov D. B., Hu S. H., Lin J., Gasch A., Hoffmann A., Horikoshi M., Chua N. H., Roeder R. G., Burley S. K. Crystal structure of TFIID TATA-box binding protein. Nature. 1992 Nov 5;360(6399):40–46. doi: 10.1038/360040a0. [DOI] [PubMed] [Google Scholar]
  30. Richter J. D., Slavicek J. M., Schneider J. F., Jones N. C. Heterogeneity of adenovirus type 5 E1A proteins: multiple serine phosphorylations induce slow-migrating electrophoretic variants but do not affect E1A-induced transcriptional activation or transformation. J Virol. 1988 Jun;62(6):1948–1955. doi: 10.1128/jvi.62.6.1948-1955.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sadowski I., Ptashne M. A vector for expressing GAL4(1-147) fusions in mammalian cells. Nucleic Acids Res. 1989 Sep 25;17(18):7539–7539. doi: 10.1093/nar/17.18.7539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Sauer F., Fondell J. D., Ohkuma Y., Roeder R. G., Jäckle H. Control of transcription by Krüppel through interactions with TFIIB and TFIIE beta. Nature. 1995 May 11;375(6527):162–164. doi: 10.1038/375162a0. [DOI] [PubMed] [Google Scholar]
  33. Tratner I., Verma I. M. Identification of a nuclear targeting sequence in the Fos protein. Oncogene. 1991 Nov;6(11):2049–2053. [PubMed] [Google Scholar]
  34. Um M., Li C., Manley J. L. The transcriptional repressor even-skipped interacts directly with TATA-binding protein. Mol Cell Biol. 1995 Sep;15(9):5007–5016. doi: 10.1128/mcb.15.9.5007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Waeber G., Habener J. F. Nuclear translocation and DNA recognition signals colocalized within the bZIP domain of cyclic adenosine 3',5'-monophosphate response element-binding protein CREB. Mol Endocrinol. 1991 Oct;5(10):1431–1438. doi: 10.1210/mend-5-10-1431. [DOI] [PubMed] [Google Scholar]
  36. Wang Z. Y., Qiu Q. Q., Gurrieri M., Huang J., Deuel T. F. WT1, the Wilms' tumor suppressor gene product, represses transcription through an interactive nuclear protein. Oncogene. 1995 Mar 16;10(6):1243–1247. [PubMed] [Google Scholar]
  37. Weintraub S. J., Chow K. N., Luo R. X., Zhang S. H., He S., Dean D. C. Mechanism of active transcriptional repression by the retinoblastoma protein. Nature. 1995 Jun 29;375(6534):812–815. doi: 10.1038/375812a0. [DOI] [PubMed] [Google Scholar]
  38. Yeung K. C., Inostroza J. A., Mermelstein F. H., Kannabiran C., Reinberg D. Structure-function analysis of the TBP-binding protein Dr1 reveals a mechanism for repression of class II gene transcription. Genes Dev. 1994 Sep 1;8(17):2097–2109. doi: 10.1101/gad.8.17.2097. [DOI] [PubMed] [Google Scholar]
  39. Zuo P., Stanojević D., Colgan J., Han K., Levine M., Manley J. L. Activation and repression of transcription by the gap proteins hunchback and Krüppel in cultured Drosophila cells. Genes Dev. 1991 Feb;5(2):254–264. doi: 10.1101/gad.5.2.254. [DOI] [PubMed] [Google Scholar]

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