Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1997 Dec;17(12):7195–7207. doi: 10.1128/mcb.17.12.7195

Constitutive activation of gene expression by thyroid hormone receptor results from reversal of p53-mediated repression.

J S Qi 1, V Desai-Yajnik 1, Y Yuan 1, H H Samuels 1
PMCID: PMC232577  PMID: 9372952

Abstract

Thyroid hormone receptor (T3R) is a member of the steroid hormone receptor gene family of nuclear hormone receptors. In most cells T3R activates gene expression only in the presence of its ligand, L-triiodothyronine (T3). However, in certain cell types (e.g., GH4C1 cells) expression of T3R leads to hormone-independent constitutive activation. This activation by unliganded T3R occurs with a variety of gene promoters and appears to be independent of the binding of T3R to specific thyroid hormone response elements (TREs). Previous studies indicate that this constitutive activation results from the titration of an inhibitor of transcription. Since the tumor suppresser p53 is capable of repressing a wide variety of gene promoters, we considered the possibility that the inhibitor is p53. Evidence to support this comes from studies indicating that expression of p53 blocks T3R-mediated constitutive activation in GH4C1 cells. In contrast with hormone-independent activation by T3R, p53 had little or no effect on T3-dependent stimulation which requires TREs. In addition, p53 mutants which oligomerize with wild-type p53 and interfere with its function also increase promoter activity. This enhancement is of similar magnitude to but is not additive with the stimulation mediated by unliganded T3R, suggesting that they target the same factor. Since p53 mutants are known to target wild-type p53 in the cell, this suggests that T3R also interacts with p53 in vivo and that endogenous levels of p53 act to suppress promoter activity. Evidence supporting both functional and physical interactions of T3R and p53 in the cell is presented. The DNA binding domain (DBD) of T3R is important in mediating constitutive activation, and the receptor DBD appears to functionally interact with the N terminus of p53 in the cell. In vitro binding studies indicate that the T3R DBD is important for interaction of T3R with p53 and that this interaction is reduced by T3. These findings are consistent with the in vivo studies indicating that p53 blocks constitutive activation but not ligand-dependent stimulation. These studies provide insight into mechanisms by which unliganded nuclear hormone receptors can modulate gene expression and may provide an explanation for the mechanism of action of the v-erbA oncoprotein, a retroviral homolog of chicken T3R alpha.

Full Text

The Full Text of this article is available as a PDF (711.2 KB).

Selected References

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

  1. Au-Fliegner M., Helmer E., Casanova J., Raaka B. M., Samuels H. H. The conserved ninth C-terminal heptad in thyroid hormone and retinoic acid receptors mediates diverse responses by affecting heterodimer but not homodimer formation. Mol Cell Biol. 1993 Sep;13(9):5725–5737. doi: 10.1128/mcb.13.9.5725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baker S. J., Markowitz S., Fearon E. R., Willson J. K., Vogelstein B. Suppression of human colorectal carcinoma cell growth by wild-type p53. Science. 1990 Aug 24;249(4971):912–915. doi: 10.1126/science.2144057. [DOI] [PubMed] [Google Scholar]
  3. 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]
  4. Baniahmad A., Leng X., Burris T. P., Tsai S. Y., Tsai M. J., O'Malley B. W. The tau 4 activation domain of the thyroid hormone receptor is required for release of a putative corepressor(s) necessary for transcriptional silencing. Mol Cell Biol. 1995 Jan;15(1):76–86. doi: 10.1128/mcb.15.1.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barak Y., Juven T., Haffner R., Oren M. mdm2 expression is induced by wild type p53 activity. EMBO J. 1993 Feb;12(2):461–468. doi: 10.1002/j.1460-2075.1993.tb05678.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bischoff J. R., Friedman P. N., Marshak D. R., Prives C., Beach D. Human p53 is phosphorylated by p60-cdc2 and cyclin B-cdc2. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4766–4770. doi: 10.1073/pnas.87.12.4766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brent G. A., Dunn M. K., Harney J. W., Gulick T., Larsen P. R., Moore D. D. Thyroid hormone aporeceptor represses T3-inducible promoters and blocks activity of the retinoic acid receptor. New Biol. 1989 Dec;1(3):329–336. [PubMed] [Google Scholar]
  8. Casanova J., Helmer E., Selmi-Ruby S., Qi J. S., Au-Fliegner M., Desai-Yajnik V., Koudinova N., Yarm F., Raaka B. M., Samuels H. H. Functional evidence for ligand-dependent dissociation of thyroid hormone and retinoic acid receptors from an inhibitory cellular factor. Mol Cell Biol. 1994 Sep;14(9):5756–5765. doi: 10.1128/mcb.14.9.5756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chatterjee V. K., Lee J. K., Rentoumis A., Jameson J. L. Negative regulation of the thyroid-stimulating hormone alpha gene by thyroid hormone: receptor interaction adjacent to the TATA box. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9114–9118. doi: 10.1073/pnas.86.23.9114. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chen J. D., Evans R. M. A transcriptional co-repressor that interacts with nuclear hormone receptors. Nature. 1995 Oct 5;377(6548):454–457. doi: 10.1038/377454a0. [DOI] [PubMed] [Google Scholar]
  11. Chiang C. M., Roeder R. G. Cloning of an intrinsic human TFIID subunit that interacts with multiple transcriptional activators. Science. 1995 Jan 27;267(5197):531–536. doi: 10.1126/science.7824954. [DOI] [PubMed] [Google Scholar]
  12. Cho Y., Gorina S., Jeffrey P. D., Pavletich N. P. Crystal structure of a p53 tumor suppressor-DNA complex: understanding tumorigenic mutations. Science. 1994 Jul 15;265(5170):346–355. doi: 10.1126/science.8023157. [DOI] [PubMed] [Google Scholar]
  13. Damm K., Thompson C. C., Evans R. M. Protein encoded by v-erbA functions as a thyroid-hormone receptor antagonist. Nature. 1989 Jun 22;339(6226):593–597. doi: 10.1038/339593a0. [DOI] [PubMed] [Google Scholar]
  14. Dayton A. I., Sodroski J. G., Rosen C. A., Goh W. C., Haseltine W. A. The trans-activator gene of the human T cell lymphotropic virus type III is required for replication. Cell. 1986 Mar 28;44(6):941–947. doi: 10.1016/0092-8674(86)90017-6. [DOI] [PubMed] [Google Scholar]
  15. Desai-Yajnik V., Hadzic E., Modlinger P., Malhotra S., Gechlik G., Samuels H. H. Interactions of thyroid hormone receptor with the human immunodeficiency virus type 1 (HIV-1) long terminal repeat and the HIV-1 Tat transactivator. J Virol. 1995 Aug;69(8):5103–5112. doi: 10.1128/jvi.69.8.5103-5112.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Desai-Yajnik V., Samuels H. H. The NF-kappa B and Sp1 motifs of the human immunodeficiency virus type 1 long terminal repeat function as novel thyroid hormone response elements. Mol Cell Biol. 1993 Aug;13(8):5057–5069. doi: 10.1128/mcb.13.8.5057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Dittmer D., Pati S., Zambetti G., Chu S., Teresky A. K., Moore M., Finlay C., Levine A. J. Gain of function mutations in p53. Nat Genet. 1993 May;4(1):42–46. doi: 10.1038/ng0593-42. [DOI] [PubMed] [Google Scholar]
  19. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fields S., Jang S. K. Presence of a potent transcription activating sequence in the p53 protein. Science. 1990 Aug 31;249(4972):1046–1049. doi: 10.1126/science.2144363. [DOI] [PubMed] [Google Scholar]
  21. Fisher A. G., Feinberg M. B., Josephs S. F., Harper M. E., Marselle L. M., Reyes G., Gonda M. A., Aldovini A., Debouk C., Gallo R. C. The trans-activator gene of HTLV-III is essential for virus replication. 1986 Mar 27-Apr 2Nature. 320(6060):367–371. doi: 10.1038/320367a0. [DOI] [PubMed] [Google Scholar]
  22. Flug F., Copp R. P., Casanova J., Horowitz Z. D., Janocko L., Plotnick M., Samuels H. H. cis-acting elements of the rat growth hormone gene which mediate basal and regulated expression by thyroid hormone. J Biol Chem. 1987 May 5;262(13):6373–6382. [PubMed] [Google Scholar]
  23. Forman B. M., Casanova J., Raaka B. M., Ghysdael J., Samuels H. H. Half-site spacing and orientation determines whether thyroid hormone and retinoic acid receptors and related factors bind to DNA response elements as monomers, homodimers, or heterodimers. Mol Endocrinol. 1992 Mar;6(3):429–442. doi: 10.1210/mend.6.3.1316541. [DOI] [PubMed] [Google Scholar]
  24. Forman B. M., Samuels H. H. Interactions among a subfamily of nuclear hormone receptors: the regulatory zipper model. Mol Endocrinol. 1990 Sep;4(9):1293–1301. doi: 10.1210/mend-4-9-1293. [DOI] [PubMed] [Google Scholar]
  25. Forman B. M., Samuels H. H. pEXPRESS: a family of expression vectors containing a single transcription unit active in prokaryotes, eukaryotes and in vitro. Gene. 1991 Aug 30;105(1):9–15. doi: 10.1016/0378-1119(91)90507-8. [DOI] [PubMed] [Google Scholar]
  26. Forman B. M., Umesono K., Chen J., Evans R. M. Unique response pathways are established by allosteric interactions among nuclear hormone receptors. Cell. 1995 May 19;81(4):541–550. doi: 10.1016/0092-8674(95)90075-6. [DOI] [PubMed] [Google Scholar]
  27. Forman B. M., Yang C. R., Au M., Casanova J., Ghysdael J., Samuels H. H. A domain containing leucine-zipper-like motifs mediate novel in vivo interactions between the thyroid hormone and retinoic acid receptors. Mol Endocrinol. 1989 Oct;3(10):1610–1626. doi: 10.1210/mend-3-10-1610. [DOI] [PubMed] [Google Scholar]
  28. Forman B. M., Yang C. R., Stanley F., Casanova J., Samuels H. H. c-erbA protooncogenes mediate thyroid hormone-dependent and independent regulation of the rat growth hormone and prolactin genes. Mol Endocrinol. 1988 Oct;2(10):902–911. doi: 10.1210/mend-2-10-902. [DOI] [PubMed] [Google Scholar]
  29. Freedman L. P. Anatomy of the steroid receptor zinc finger region. Endocr Rev. 1992 May;13(2):129–145. doi: 10.1210/edrv-13-2-129. [DOI] [PubMed] [Google Scholar]
  30. Ginsberg D., Mechta F., Yaniv M., Oren M. Wild-type p53 can down-modulate the activity of various promoters. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9979–9983. doi: 10.1073/pnas.88.22.9979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Hadzic E., Desai-Yajnik V., Helmer E., Guo S., Wu S., Koudinova N., Casanova J., Raaka B. M., Samuels H. H. A 10-amino-acid sequence in the N-terminal A/B domain of thyroid hormone receptor alpha is essential for transcriptional activation and interaction with the general transcription factor TFIIB. Mol Cell Biol. 1995 Aug;15(8):4507–4517. doi: 10.1128/mcb.15.8.4507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Haines D. S., Landers J. E., Engle L. J., George D. L. Physical and functional interaction between wild-type p53 and mdm2 proteins. Mol Cell Biol. 1994 Feb;14(2):1171–1178. doi: 10.1128/mcb.14.2.1171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Harvey M., Vogel H., Morris D., Bradley A., Bernstein A., Donehower L. A. A mutant p53 transgene accelerates tumour development in heterozygous but not nullizygous p53-deficient mice. Nat Genet. 1995 Mar;9(3):305–311. doi: 10.1038/ng0395-305. [DOI] [PubMed] [Google Scholar]
  34. Haupt Y., Barak Y., Oren M. Cell type-specific inhibition of p53-mediated apoptosis by mdm2. EMBO J. 1996 Apr 1;15(7):1596–1606. [PMC free article] [PubMed] [Google Scholar]
  35. Helmer E. B., Raaka B. M., Samuels H. H. Hormone-dependent and -independent transcriptional activation by thyroid hormone receptors are mediated by different mechanisms. Endocrinology. 1996 Feb;137(2):390–399. doi: 10.1210/endo.137.2.8593781. [DOI] [PubMed] [Google Scholar]
  36. Herrmann C. H., Rice A. P. Specific interaction of the human immunodeficiency virus Tat proteins with a cellular protein kinase. Virology. 1993 Dec;197(2):601–608. doi: 10.1006/viro.1993.1634. [DOI] [PubMed] [Google Scholar]
  37. Hodin R. A., Lazar M. A., Wintman B. I., Darling D. S., Koenig R. J., Larsen P. R., Moore D. D., Chin W. W. Identification of a thyroid hormone receptor that is pituitary-specific. Science. 1989 Apr 7;244(4900):76–79. doi: 10.1126/science.2539642. [DOI] [PubMed] [Google Scholar]
  38. Horowitz Z. D., Yang C. R., Forman B. M., Casanova J., Samuels H. H. Characterization of the domain structure of chick c-erbA by deletion mutation: in vitro translation and cell transfection studies. Mol Endocrinol. 1989 Jan;3(1):148–156. doi: 10.1210/mend-3-1-148. [DOI] [PubMed] [Google Scholar]
  39. 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]
  40. Juven T., Barak Y., Zauberman A., George D. L., Oren M. Wild type p53 can mediate sequence-specific transactivation of an internal promoter within the mdm2 gene. Oncogene. 1993 Dec;8(12):3411–3416. [PubMed] [Google Scholar]
  41. Kastan M. B., Zhan Q., el-Deiry W. S., Carrier F., Jacks T., Walsh W. V., Plunkett B. S., Vogelstein B., Fornace A. J., Jr A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell. 1992 Nov 13;71(4):587–597. doi: 10.1016/0092-8674(92)90593-2. [DOI] [PubMed] [Google Scholar]
  42. Kern S. E., Kinzler K. W., Bruskin A., Jarosz D., Friedman P., Prives C., Vogelstein B. Identification of p53 as a sequence-specific DNA-binding protein. Science. 1991 Jun 21;252(5013):1708–1711. doi: 10.1126/science.2047879. [DOI] [PubMed] [Google Scholar]
  43. Kern S. E., Pietenpol J. A., Thiagalingam S., Seymour A., Kinzler K. W., Vogelstein B. Oncogenic forms of p53 inhibit p53-regulated gene expression. Science. 1992 May 8;256(5058):827–830. doi: 10.1126/science.1589764. [DOI] [PubMed] [Google Scholar]
  44. Ko L. J., Prives C. p53: puzzle and paradigm. Genes Dev. 1996 May 1;10(9):1054–1072. doi: 10.1101/gad.10.9.1054. [DOI] [PubMed] [Google Scholar]
  45. Landers J. E., Haines D. S., Strauss J. F., 3rd, George D. L. Enhanced translation: a novel mechanism of mdm2 oncogene overexpression identified in human tumor cells. Oncogene. 1994 Sep;9(9):2745–2750. [PubMed] [Google Scholar]
  46. Lane D. P., Crawford L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. doi: 10.1038/278261a0. [DOI] [PubMed] [Google Scholar]
  47. Lazar M. A. Thyroid hormone receptors: multiple forms, multiple possibilities. Endocr Rev. 1993 Apr;14(2):184–193. doi: 10.1210/edrv-14-2-184. [DOI] [PubMed] [Google Scholar]
  48. Lee J. W., Ryan F., Swaffield J. C., Johnston S. A., Moore D. D. Interaction of thyroid-hormone receptor with a conserved transcriptional mediator. Nature. 1995 Mar 2;374(6517):91–94. doi: 10.1038/374091a0. [DOI] [PubMed] [Google Scholar]
  49. Lezoualc'h F., Hassan A. H., Giraud P., Loeffler J. P., Lee S. L., Demeneix B. A. Assignment of the beta-thyroid hormone receptor to 3,5,3'-triiodothyronine-dependent inhibition of transcription from the thyrotropin-releasing hormone promoter in chick hypothalamic neurons. Mol Endocrinol. 1992 Nov;6(11):1797–1804. doi: 10.1210/mend.6.11.1480171. [DOI] [PubMed] [Google Scholar]
  50. 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]
  51. Lin J., Chen J., Elenbaas B., Levine A. J. Several hydrophobic amino acids in the p53 amino-terminal domain are required for transcriptional activation, binding to mdm-2 and the adenovirus 5 E1B 55-kD protein. Genes Dev. 1994 May 15;8(10):1235–1246. doi: 10.1101/gad.8.10.1235. [DOI] [PubMed] [Google Scholar]
  52. Linzer D. I., Levine A. J. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43–52. doi: 10.1016/0092-8674(79)90293-9. [DOI] [PubMed] [Google Scholar]
  53. Liu X., Miller C. W., Koeffler P. H., Berk A. J. The p53 activation domain binds the TATA box-binding polypeptide in Holo-TFIID, and a neighboring p53 domain inhibits transcription. Mol Cell Biol. 1993 Jun;13(6):3291–3300. doi: 10.1128/mcb.13.6.3291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Mack D. H., Vartikar J., Pipas J. M., Laimins L. A. Specific repression of TATA-mediated but not initiator-mediated transcription by wild-type p53. Nature. 1993 May 20;363(6426):281–283. doi: 10.1038/363281a0. [DOI] [PubMed] [Google Scholar]
  55. Maheswaran S., Englert C., Bennett P., Heinrich G., Haber D. A. The WT1 gene product stabilizes p53 and inhibits p53-mediated apoptosis. Genes Dev. 1995 Sep 1;9(17):2143–2156. doi: 10.1101/gad.9.17.2143. [DOI] [PubMed] [Google Scholar]
  56. Mangelsdorf D. J., Thummel C., Beato M., Herrlich P., Schütz G., Umesono K., Blumberg B., Kastner P., Mark M., Chambon P. The nuclear receptor superfamily: the second decade. Cell. 1995 Dec 15;83(6):835–839. doi: 10.1016/0092-8674(95)90199-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Masuda H., Miller C., Koeffler H. P., Battifora H., Cline M. J. Rearrangement of the p53 gene in human osteogenic sarcomas. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7716–7719. doi: 10.1073/pnas.84.21.7716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Morris G. F., Mathews M. B. The adenovirus E1A transforming protein activates the proliferating cell nuclear antigen promoter via an activating transcription factor site. J Virol. 1991 Dec;65(12):6397–6406. doi: 10.1128/jvi.65.12.6397-6406.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Muñoz A., Zenke M., Gehring U., Sap J., Beug H., Vennström B. Characterization of the hormone-binding domain of the chicken c-erbA/thyroid hormone receptor protein. EMBO J. 1988 Jan;7(1):155–159. doi: 10.1002/j.1460-2075.1988.tb02795.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. O'Shea-Greenfield A., Smale S. T. Roles of TATA and initiator elements in determining the start site location and direction of RNA polymerase II transcription. J Biol Chem. 1992 Jan 15;267(2):1391–1402. [PubMed] [Google Scholar]
  61. Oren M., Maltzman W., Levine A. J. Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells. Mol Cell Biol. 1981 Feb;1(2):101–110. doi: 10.1128/mcb.1.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Oñate S. A., Tsai S. Y., Tsai M. J., O'Malley B. W. Sequence and characterization of a coactivator for the steroid hormone receptor superfamily. Science. 1995 Nov 24;270(5240):1354–1357. doi: 10.1126/science.270.5240.1354. [DOI] [PubMed] [Google Scholar]
  63. Pinhasi-Kimhi O., Michalovitz D., Ben-Zeev A., Oren M. Specific interaction between the p53 cellular tumour antigen and major heat shock proteins. Nature. 1986 Mar 13;320(6058):182–184. doi: 10.1038/320182a0. [DOI] [PubMed] [Google Scholar]
  64. Qi J. S., Desai-Yajnik V., Greene M. E., Raaka B. M., Samuels H. H. The ligand-binding domains of the thyroid hormone/retinoid receptor gene subfamily function in vivo to mediate heterodimerization, gene silencing, and transactivation. Mol Cell Biol. 1995 Mar;15(3):1817–1825. doi: 10.1128/mcb.15.3.1817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Qin X. Q., Chittenden T., Livingston D. M., Kaelin W. G., Jr Identification of a growth suppression domain within the retinoblastoma gene product. Genes Dev. 1992 Jun;6(6):953–964. doi: 10.1101/gad.6.6.953. [DOI] [PubMed] [Google Scholar]
  66. Reich N. C., Oren M., Levine A. J. Two distinct mechanisms regulate the levels of a cellular tumor antigen, p53. Mol Cell Biol. 1983 Dec;3(12):2143–2150. doi: 10.1128/mcb.3.12.2143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Rhim H., Echetebu C. O., Herrmann C. H., Rice A. P. Wild-type and mutant HIV-1 and HIV-2 Tat proteins expressed in Escherichia coli as fusions with glutathione S-transferase. J Acquir Immune Defic Syndr. 1994 Nov;7(11):1116–1121. [PubMed] [Google Scholar]
  68. Saatcioglu F., Deng T., Karin M. A novel cis element mediating ligand-independent activation by c-ErbA: implications for hormonal regulation. Cell. 1993 Dec 17;75(6):1095–1105. doi: 10.1016/0092-8674(93)90319-l. [DOI] [PubMed] [Google Scholar]
  69. Sabbatini P., Chiou S. K., Rao L., White E. Modulation of p53-mediated transcriptional repression and apoptosis by the adenovirus E1B 19K protein. Mol Cell Biol. 1995 Feb;15(2):1060–1070. doi: 10.1128/mcb.15.2.1060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Santhanam U., Ray A., Sehgal P. B. Repression of the interleukin 6 gene promoter by p53 and the retinoblastoma susceptibility gene product. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7605–7609. doi: 10.1073/pnas.88.17.7605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Sap J., Muñoz A., Damm K., Goldberg Y., Ghysdael J., Leutz A., Beug H., Vennström B. The c-erb-A protein is a high-affinity receptor for thyroid hormone. Nature. 1986 Dec 18;324(6098):635–640. doi: 10.1038/324635a0. [DOI] [PubMed] [Google Scholar]
  72. Schaufele F., West B. L., Baxter J. D. Synergistic activation of the rat growth hormone promoter by Pit-1 and the thyroid hormone receptor. Mol Endocrinol. 1992 Apr;6(4):656–665. doi: 10.1210/mend.6.4.1584227. [DOI] [PubMed] [Google Scholar]
  73. Scheffner M., Werness B. A., Huibregtse J. M., Levine A. J., Howley P. M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell. 1990 Dec 21;63(6):1129–1136. doi: 10.1016/0092-8674(90)90409-8. [DOI] [PubMed] [Google Scholar]
  74. Selmi S., Samuels H. H. Thyroid hormone receptor/and v-erbA. A single amino acid difference in the C-terminal region influences dominant negative activity and receptor dimer formation. J Biol Chem. 1991 Jun 25;266(18):11589–11593. [PubMed] [Google Scholar]
  75. Selvakumaran M., Lin H. K., Miyashita T., Wang H. G., Krajewski S., Reed J. C., Hoffman B., Liebermann D. Immediate early up-regulation of bax expression by p53 but not TGF beta 1: a paradigm for distinct apoptotic pathways. Oncogene. 1994 Jun;9(6):1791–1798. [PubMed] [Google Scholar]
  76. Shaulian E., Zauberman A., Ginsberg D., Oren M. Identification of a minimal transforming domain of p53: negative dominance through abrogation of sequence-specific DNA binding. Mol Cell Biol. 1992 Dec;12(12):5581–5592. doi: 10.1128/mcb.12.12.5581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Shiio Y., Yamamoto T., Yamaguchi N. Negative regulation of Rb expression by the p53 gene product. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5206–5210. doi: 10.1073/pnas.89.12.5206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Smit-McBride Z., Privalsky M. L. DNA sequence specificity of the v-erb A oncoprotein/thyroid hormone receptor: role of the P-box and its interaction with more N-terminal determinants of DNA recognition. Mol Endocrinol. 1994 Jul;8(7):819–828. doi: 10.1210/mend.8.7.7984144. [DOI] [PubMed] [Google Scholar]
  79. Smith D. B., Johnson K. S. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. Gene. 1988 Jul 15;67(1):31–40. doi: 10.1016/0378-1119(88)90005-4. [DOI] [PubMed] [Google Scholar]
  80. Soussi T., Caron de Fromentel C., May P. Structural aspects of the p53 protein in relation to gene evolution. Oncogene. 1990 Jul;5(7):945–952. [PubMed] [Google Scholar]
  81. Stall R., McKusick L., Wiley J., Coates T. J., Ostrow D. G. Alcohol and drug use during sexual activity and compliance with safe sex guidelines for AIDS: the AIDS Behavioral Research Project. Health Educ Q. 1986 Winter;13(4):359–371. doi: 10.1177/109019818601300407. [DOI] [PubMed] [Google Scholar]
  82. Stürzbecher H. W., Brain R., Addison C., Rudge K., Remm M., Grimaldi M., Keenan E., Jenkins J. R. A C-terminal alpha-helix plus basic region motif is the major structural determinant of p53 tetramerization. Oncogene. 1992 Aug;7(8):1513–1523. [PubMed] [Google Scholar]
  83. Subler M. A., Martin D. W., Deb S. Overlapping domains on the p53 protein regulate its transcriptional activation and repression functions. Oncogene. 1994 May;9(5):1351–1359. [PubMed] [Google Scholar]
  84. Szekely L., Selivanova G., Magnusson K. P., Klein G., Wiman K. G. EBNA-5, an Epstein-Barr virus-encoded nuclear antigen, binds to the retinoblastoma and p53 proteins. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5455–5459. doi: 10.1073/pnas.90.12.5455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Tanaka M., Gupta R., Mayer B. J. Differential inhibition of signaling pathways by dominant-negative SH2/SH3 adapter proteins. Mol Cell Biol. 1995 Dec;15(12):6829–6837. doi: 10.1128/mcb.15.12.6829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Thomas M., Matlashewski G., Pim D., Banks L. Induction of apoptosis by p53 is independent of its oligomeric state and can be abolished by HPV-18 E6 through ubiquitin mediated degradation. Oncogene. 1996 Jul 18;13(2):265–273. [PubMed] [Google Scholar]
  87. Tomic M., Jiang C. K., Epstein H. S., Freedberg I. M., Samuels H. H., Blumenberg M. Nuclear receptors for retinoic acid and thyroid hormone regulate transcription of keratin genes. Cell Regul. 1990 Nov;1(12):965–973. doi: 10.1091/mbc.1.12.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Tomić-Canić M., Day D., Samuels H. H., Freedberg I. M., Blumenberg M. Novel regulation of keratin gene expression by thyroid hormone and retinoid receptors. J Biol Chem. 1996 Jan 19;271(3):1416–1423. doi: 10.1074/jbc.271.3.1416. [DOI] [PubMed] [Google Scholar]
  89. Umesono K., Giguere V., Glass C. K., Rosenfeld M. G., Evans R. M. Retinoic acid and thyroid hormone induce gene expression through a common responsive element. Nature. 1988 Nov 17;336(6196):262–265. doi: 10.1038/336262a0. [DOI] [PubMed] [Google Scholar]
  90. Umesono K., Murakami K. K., Thompson C. C., Evans R. M. Direct repeats as selective response elements for the thyroid hormone, retinoic acid, and vitamin D3 receptors. Cell. 1991 Jun 28;65(7):1255–1266. doi: 10.1016/0092-8674(91)90020-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Wang Y., Reed M., Wang P., Stenger J. E., Mayr G., Anderson M. E., Schwedes J. F., Tegtmeyer P. p53 domains: identification and characterization of two autonomous DNA-binding regions. Genes Dev. 1993 Dec;7(12B):2575–2586. doi: 10.1101/gad.7.12b.2575. [DOI] [PubMed] [Google Scholar]
  92. Ways D. K., Qin W., Cook P., Parker P. J., Menke J. B., Hao E., Smith A. M., Jones C., Hershman J. M., Geffner M. E. Dominant and nondominant negative C-erbA beta 1 receptors associated with thyroid hormone resistance syndromes augment 12-O-tetradecanoyl-phorbol-13-acetate induction of the collagenase promoter and exhibit defective 3,5,3'-triiodothyronine-mediated repression. Mol Endocrinol. 1993 Sep;7(9):1112–1120. doi: 10.1210/mend.7.9.8247013. [DOI] [PubMed] [Google Scholar]
  93. Weinberger C., Thompson C. C., Ong E. S., Lebo R., Gruol D. J., Evans R. M. The c-erb-A gene encodes a thyroid hormone receptor. Nature. 1986 Dec 18;324(6098):641–646. doi: 10.1038/324641a0. [DOI] [PubMed] [Google Scholar]
  94. Weintraub H., Hauschka S., Tapscott S. J. The MCK enhancer contains a p53 responsive element. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4570–4571. doi: 10.1073/pnas.88.11.4570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Werness B. A., Levine A. J., Howley P. M. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science. 1990 Apr 6;248(4951):76–79. doi: 10.1126/science.2157286. [DOI] [PubMed] [Google Scholar]
  96. Wu X., Bayle J. H., Olson D., Levine A. J. The p53-mdm-2 autoregulatory feedback loop. Genes Dev. 1993 Jul;7(7A):1126–1132. doi: 10.1101/gad.7.7a.1126. [DOI] [PubMed] [Google Scholar]
  97. Yamamoto M., Yoshida M., Ono K., Fujita T., Ohtani-Fujita N., Sakai T., Nikaido T. Effect of tumor suppressors on cell cycle-regulatory genes: RB suppresses p34cdc2 expression and normal p53 suppresses cyclin A expression. Exp Cell Res. 1994 Jan;210(1):94–101. doi: 10.1006/excr.1994.1014. [DOI] [PubMed] [Google Scholar]
  98. Yap N., Yu C. L., Cheng S. Y. Modulation of the transcriptional activity of thyroid hormone receptors by the tumor suppressor p53. Proc Natl Acad Sci U S A. 1996 Apr 30;93(9):4273–4277. doi: 10.1073/pnas.93.9.4273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Yew P. R., Berk A. J. Inhibition of p53 transactivation required for transformation by adenovirus early 1B protein. Nature. 1992 May 7;357(6373):82–85. doi: 10.1038/357082a0. [DOI] [PubMed] [Google Scholar]
  100. Yonish-Rouach E., Grunwald D., Wilder S., Kimchi A., May E., Lawrence J. J., May P., Oren M. p53-mediated cell death: relationship to cell cycle control. Mol Cell Biol. 1993 Mar;13(3):1415–1423. doi: 10.1128/mcb.13.3.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Zambetti G. P., Bargonetti J., Walker K., Prives C., Levine A. J. Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element. Genes Dev. 1992 Jul;6(7):1143–1152. doi: 10.1101/gad.6.7.1143. [DOI] [PubMed] [Google Scholar]
  102. Zenke M., Muñoz A., Sap J., Vennström B., Beug H. v-erbA oncogene activation entails the loss of hormone-dependent regulator activity of c-erbA. Cell. 1990 Jun 15;61(6):1035–1049. doi: 10.1016/0092-8674(90)90068-p. [DOI] [PubMed] [Google Scholar]
  103. el-Deiry W. S., Tokino T., Velculescu V. E., Levy D. B., Parsons R., Trent J. M., Lin D., Mercer W. E., Kinzler K. W., Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993 Nov 19;75(4):817–825. doi: 10.1016/0092-8674(93)90500-p. [DOI] [PubMed] [Google Scholar]

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

RESOURCES