Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1994 Dec 15;13(24):5967–5976. doi: 10.1002/j.1460-2075.1994.tb06942.x

Transformation by homeobox genes can be mediated by selective transcriptional repression.

X F Qin 1, Y Luo 1, H Suh 1, J Wayne 1, Z Misulovin 1, R G Roeder 1, M C Nussenzweig 1
PMCID: PMC395572  PMID: 7813434

Abstract

Altered transcription is a recurrent theme in the field of cancer biology. But despite the central role of transcription in transformation, little is known about the mechanism by which dominant nuclear oncogenes induce malignancies. Homeobox family proteins are prominent examples of transcriptional regulators which control development and can function as oncogenes. Here we explore the molecular basis for transformation by this class of regulators using Oct-2 and Oct-1. We show that the DNA binding POU domains of these proteins are selective and sequence-specific transcriptional repressors that produce malignant lymphomas when they are expressed in T cells of transgenic mice. Mutagenesis experiments identified a specific set of promoters, those containing octamer regulatory elements, as the targets for transformation by selective inhibition of gene expression.

Full text

PDF
5967

Images in this article

Selected References

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

  1. Adams J. M., Cory S. Transgenic models of tumor development. Science. 1991 Nov 22;254(5035):1161–1167. doi: 10.1126/science.1957168. [DOI] [PubMed] [Google Scholar]
  2. Adams J. M., Harris A. W., Pinkert C. A., Corcoran L. M., Alexander W. S., Cory S., Palmiter R. D., Brinster R. L. The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature. 1985 Dec 12;318(6046):533–538. doi: 10.1038/318533a0. [DOI] [PubMed] [Google Scholar]
  3. Amati B., Dalton S., Brooks M. W., Littlewood T. D., Evan G. I., Land H. Transcriptional activation by the human c-Myc oncoprotein in yeast requires interaction with Max. Nature. 1992 Oct 1;359(6394):423–426. doi: 10.1038/359423a0. [DOI] [PubMed] [Google Scholar]
  4. Assa-Munt N., Mortishire-Smith R. J., Aurora R., Herr W., Wright P. E. The solution structure of the Oct-1 POU-specific domain reveals a striking similarity to the bacteriophage lambda repressor DNA-binding domain. Cell. 1993 Apr 9;73(1):193–205. doi: 10.1016/0092-8674(93)90171-l. [DOI] [PubMed] [Google Scholar]
  5. Ayer D. E., Kretzner L., Eisenman R. N. Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity. Cell. 1993 Jan 29;72(2):211–222. doi: 10.1016/0092-8674(93)90661-9. [DOI] [PubMed] [Google Scholar]
  6. Ballard D. W., Walker W. H., Doerre S., Sista P., Molitor J. A., Dixon E. P., Peffer N. J., Hannink M., Greene W. C. The v-rel oncogene encodes a kappa B enhancer binding protein that inhibits NF-kappa B function. Cell. 1990 Nov 16;63(4):803–814. doi: 10.1016/0092-8674(90)90146-6. [DOI] [PubMed] [Google Scholar]
  7. Bishop J. M. Molecular themes in oncogenesis. Cell. 1991 Jan 25;64(2):235–248. doi: 10.1016/0092-8674(91)90636-d. [DOI] [PubMed] [Google Scholar]
  8. Blackwood E. M., Eisenman R. N. Max: a helix-loop-helix zipper protein that forms a sequence-specific DNA-binding complex with Myc. Science. 1991 Mar 8;251(4998):1211–1217. doi: 10.1126/science.2006410. [DOI] [PubMed] [Google Scholar]
  9. Blatt C., Aberdam D., Schwartz R., Sachs L. DNA rearrangement of a homeobox gene in myeloid leukaemic cells. EMBO J. 1988 Dec 20;7(13):4283–4290. doi: 10.1002/j.1460-2075.1988.tb03326.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Chaffin K. E., Beals C. R., Wilkie T. M., Forbush K. A., Simon M. I., Perlmutter R. M. Dissection of thymocyte signaling pathways by in vivo expression of pertussis toxin ADP-ribosyltransferase. EMBO J. 1990 Dec;9(12):3821–3829. doi: 10.1002/j.1460-2075.1990.tb07600.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cleary M. A., Stern S., Tanaka M., Herr W. Differential positive control by Oct-1 and Oct-2: activation of a transcriptionally silent motif through Oct-1 and VP16 corecruitment. Genes Dev. 1993 Jan;7(1):72–83. doi: 10.1101/gad.7.1.72. [DOI] [PubMed] [Google Scholar]
  12. Cleary M. L. Oncogenic conversion of transcription factors by chromosomal translocations. Cell. 1991 Aug 23;66(4):619–622. doi: 10.1016/0092-8674(91)90105-8. [DOI] [PubMed] [Google Scholar]
  13. Clerc R. G., Corcoran L. M., LeBowitz J. H., Baltimore D., Sharp P. A. The B-cell-specific Oct-2 protein contains POU box- and homeo box-type domains. Genes Dev. 1988 Dec;2(12A):1570–1581. doi: 10.1101/gad.2.12a.1570. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Dedera D. A., Waller E. K., LeBrun D. P., Sen-Majumdar A., Stevens M. E., Barsh G. S., Cleary M. L. Chimeric homeobox gene E2A-PBX1 induces proliferation, apoptosis, and malignant lymphomas in transgenic mice. Cell. 1993 Sep 10;74(5):833–843. doi: 10.1016/0092-8674(93)90463-z. [DOI] [PubMed] [Google Scholar]
  16. Dekker N., Cox M., Boelens R., Verrijzer C. P., van der Vliet P. C., Kaptein R. Solution structure of the POU-specific DNA-binding domain of Oct-1. Nature. 1993 Apr 29;362(6423):852–855. doi: 10.1038/362852a0. [DOI] [PubMed] [Google Scholar]
  17. Desbois C., Aubert D., Legrand C., Pain B., Samarut J. A novel mechanism of action for v-ErbA: abrogation of the inactivation of transcription factor AP-1 by retinoic acid and thyroid hormone receptors. Cell. 1991 Nov 15;67(4):731–740. doi: 10.1016/0092-8674(91)90068-a. [DOI] [PubMed] [Google Scholar]
  18. Desplan C., Theis J., O'Farrell P. H. The sequence specificity of homeodomain-DNA interaction. Cell. 1988 Sep 23;54(7):1081–1090. doi: 10.1016/0092-8674(88)90123-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Ekker S. C., Young K. E., von Kessler D. P., Beachy P. A. Optimal DNA sequence recognition by the Ultrabithorax homeodomain of Drosophila. EMBO J. 1991 May;10(5):1179–1186. doi: 10.1002/j.1460-2075.1991.tb08058.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fenton R. G., Marrack P., Kappler J. W., Kanagawa O., Seidman J. G. Isotypic exclusion of gamma delta T cell receptors in transgenic mice bearing a rearranged beta-chain gene. Science. 1988 Aug 26;241(4869):1089–1092. doi: 10.1126/science.2970670. [DOI] [PubMed] [Google Scholar]
  21. Garvin A. M., Abraham K. M., Forbush K. A., Farr A. G., Davison B. L., Perlmutter R. M. Disruption of thymocyte development and lymphomagenesis induced by SV40 T-antigen. Int Immunol. 1990;2(2):173–180. doi: 10.1093/intimm/2.2.173. [DOI] [PubMed] [Google Scholar]
  22. Gerster T., Balmaceda C. G., Roeder R. G. The cell type-specific octamer transcription factor OTF-2 has two domains required for the activation of transcription. EMBO J. 1990 May;9(5):1635–1643. doi: 10.1002/j.1460-2075.1990.tb08283.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Gerster T., Roeder R. G. A herpesvirus trans-activating protein interacts with transcription factor OTF-1 and other cellular proteins. Proc Natl Acad Sci U S A. 1988 Sep;85(17):6347–6351. doi: 10.1073/pnas.85.17.6347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Gregor P. D., Sawadogo M., Roeder R. G. The adenovirus major late transcription factor USF is a member of the helix-loop-helix group of regulatory proteins and binds to DNA as a dimer. Genes Dev. 1990 Oct;4(10):1730–1740. doi: 10.1101/gad.4.10.1730. [DOI] [PubMed] [Google Scholar]
  25. Harper J. W., Adami G. R., Wei N., Keyomarsi K., Elledge S. J. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993 Nov 19;75(4):805–816. doi: 10.1016/0092-8674(93)90499-g. [DOI] [PubMed] [Google Scholar]
  26. Hatano M., Roberts C. W., Minden M., Crist W. M., Korsmeyer S. J. Deregulation of a homeobox gene, HOX11, by the t(10;14) in T cell leukemia. Science. 1991 Jul 5;253(5015):79–82. doi: 10.1126/science.1676542. [DOI] [PubMed] [Google Scholar]
  27. Hatzopoulos A. K., Stoykova A. S., Erselius J. R., Goulding M., Neuman T., Gruss P. Structure and expression of the mouse Oct2a and Oct2b, two differentially spliced products of the same gene. Development. 1990 Jun;109(2):349–362. doi: 10.1242/dev.109.2.349. [DOI] [PubMed] [Google Scholar]
  28. Herr W., Sturm R. A., Clerc R. G., Corcoran L. M., Baltimore D., Sharp P. A., Ingraham H. A., Rosenfeld M. G., Finney M., Ruvkun G. The POU domain: a large conserved region in the mammalian pit-1, oct-1, oct-2, and Caenorhabditis elegans unc-86 gene products. Genes Dev. 1988 Dec;2(12A):1513–1516. doi: 10.1101/gad.2.12a.1513. [DOI] [PubMed] [Google Scholar]
  29. Hoffmann A., Roeder R. G. Purification of his-tagged proteins in non-denaturing conditions suggests a convenient method for protein interaction studies. Nucleic Acids Res. 1991 Nov 25;19(22):6337–6338. doi: 10.1093/nar/19.22.6337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Hunter T. Cooperation between oncogenes. Cell. 1991 Jan 25;64(2):249–270. doi: 10.1016/0092-8674(91)90637-e. [DOI] [PubMed] [Google Scholar]
  31. Ingraham H. A., Flynn S. E., Voss J. W., Albert V. R., Kapiloff M. S., Wilson L., Rosenfeld M. G. The POU-specific domain of Pit-1 is essential for sequence-specific, high affinity DNA binding and DNA-dependent Pit-1-Pit-1 interactions. Cell. 1990 Jun 15;61(6):1021–1033. doi: 10.1016/0092-8674(90)90067-o. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Kakizuka A., Miller W. H., Jr, Umesono K., Warrell R. P., Jr, Frankel S. R., Murty V. V., Dmitrovsky E., Evans R. M. Chromosomal translocation t(15;17) in human acute promyelocytic leukemia fuses RAR alpha with a novel putative transcription factor, PML. Cell. 1991 Aug 23;66(4):663–674. doi: 10.1016/0092-8674(91)90112-c. [DOI] [PubMed] [Google Scholar]
  34. Kamps M. P., Look A. T., Baltimore D. The human t(1;19) translocation in pre-B ALL produces multiple nuclear E2A-Pbx1 fusion proteins with differing transforming potentials. Genes Dev. 1991 Mar;5(3):358–368. doi: 10.1101/gad.5.3.358. [DOI] [PubMed] [Google Scholar]
  35. Kamps M. P., Murre C., Sun X. H., Baltimore D. A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL. Cell. 1990 Feb 23;60(4):547–555. doi: 10.1016/0092-8674(90)90658-2. [DOI] [PubMed] [Google Scholar]
  36. Kennedy M. A., Gonzalez-Sarmiento R., Kees U. R., Lampert F., Dear N., Boehm T., Rabbitts T. H. HOX11, a homeobox-containing T-cell oncogene on human chromosome 10q24. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8900–8904. doi: 10.1073/pnas.88.20.8900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. Klemm J. D., Rould M. A., Aurora R., Herr W., Pabo C. O. Crystal structure of the Oct-1 POU domain bound to an octamer site: DNA recognition with tethered DNA-binding modules. Cell. 1994 Apr 8;77(1):21–32. doi: 10.1016/0092-8674(94)90231-3. [DOI] [PubMed] [Google Scholar]
  39. Ko H. S., Fast P., McBride W., Staudt L. M. A human protein specific for the immunoglobulin octamer DNA motif contains a functional homeobox domain. Cell. 1988 Oct 7;55(1):135–144. doi: 10.1016/0092-8674(88)90016-5. [DOI] [PubMed] [Google Scholar]
  40. Kongsuwan K., Allen J., Adams J. M. Expression of Hox-2.4 homeobox gene directed by proviral insertion in a myeloid leukemia. Nucleic Acids Res. 1989 Mar 11;17(5):1881–1892. doi: 10.1093/nar/17.5.1881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Kretzner L., Blackwood E. M., Eisenman R. N. Myc and Max proteins possess distinct transcriptional activities. Nature. 1992 Oct 1;359(6394):426–429. doi: 10.1038/359426a0. [DOI] [PubMed] [Google Scholar]
  42. Kristie T. M., LeBowitz J. H., Sharp P. A. The octamer-binding proteins form multi-protein--DNA complexes with the HSV alpha TIF regulatory protein. EMBO J. 1989 Dec 20;8(13):4229–4238. doi: 10.1002/j.1460-2075.1989.tb08608.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Kunkel T. A. Rapid and efficient site-specific mutagenesis without phenotypic selection. Proc Natl Acad Sci U S A. 1985 Jan;82(2):488–492. doi: 10.1073/pnas.82.2.488. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Lai J. S., Cleary M. A., Herr W. A single amino acid exchange transfers VP16-induced positive control from the Oct-1 to the Oct-2 homeo domain. Genes Dev. 1992 Nov;6(11):2058–2065. doi: 10.1101/gad.6.11.2058. [DOI] [PubMed] [Google Scholar]
  45. LeBowitz J. H., Kobayashi T., Staudt L., Baltimore D., Sharp P. A. Octamer-binding proteins from B or HeLa cells stimulate transcription of the immunoglobulin heavy-chain promoter in vitro. Genes Dev. 1988 Oct;2(10):1227–1237. doi: 10.1101/gad.2.10.1227. [DOI] [PubMed] [Google Scholar]
  46. LeBrun D. P., Cleary M. L. Fusion with E2A alters the transcriptional properties of the homeodomain protein PBX1 in t(1;19) leukemias. Oncogene. 1994 Jun;9(6):1641–1647. [PubMed] [Google Scholar]
  47. Levine M., Hoey T. Homeobox proteins as sequence-specific transcription factors. Cell. 1988 Nov 18;55(4):537–540. doi: 10.1016/0092-8674(88)90209-7. [DOI] [PubMed] [Google Scholar]
  48. Lewin B. Oncogenic conversion by regulatory changes in transcription factors. Cell. 1991 Jan 25;64(2):303–312. doi: 10.1016/0092-8674(91)90640-k. [DOI] [PubMed] [Google Scholar]
  49. Lu M., Gong Z. Y., Shen W. F., Ho A. D. The tcl-3 proto-oncogene altered by chromosomal translocation in T-cell leukemia codes for a homeobox protein. EMBO J. 1991 Oct;10(10):2905–2910. doi: 10.1002/j.1460-2075.1991.tb07840.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Lu Q., Wright D. D., Kamps M. P. Fusion with E2A converts the Pbx1 homeodomain protein into a constitutive transcriptional activator in human leukemias carrying the t(1;19) translocation. Mol Cell Biol. 1994 Jun;14(6):3938–3948. doi: 10.1128/mcb.14.6.3938. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Luo Y., Fujii H., Gerster T., Roeder R. G. A novel B cell-derived coactivator potentiates the activation of immunoglobulin promoters by octamer-binding transcription factors. Cell. 1992 Oct 16;71(2):231–241. doi: 10.1016/0092-8674(92)90352-d. [DOI] [PubMed] [Google Scholar]
  52. Marshall C. J. Tumor suppressor genes. Cell. 1991 Jan 25;64(2):313–326. doi: 10.1016/0092-8674(91)90641-b. [DOI] [PubMed] [Google Scholar]
  53. Maulbecker C. C., Gruss P. The oncogenic potential of Pax genes. EMBO J. 1993 Jun;12(6):2361–2367. doi: 10.1002/j.1460-2075.1993.tb05890.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. McGinnis W., Krumlauf R. Homeobox genes and axial patterning. Cell. 1992 Jan 24;68(2):283–302. doi: 10.1016/0092-8674(92)90471-n. [DOI] [PubMed] [Google Scholar]
  55. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Monica K., Galili N., Nourse J., Saltman D., Cleary M. L. PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1. Mol Cell Biol. 1991 Dec;11(12):6149–6157. doi: 10.1128/mcb.11.12.6149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Murphy S., Yoon J. B., Gerster T., Roeder R. G. Oct-1 and Oct-2 potentiate functional interactions of a transcription factor with the proximal sequence element of small nuclear RNA genes. Mol Cell Biol. 1992 Jul;12(7):3247–3261. doi: 10.1128/mcb.12.7.3247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Müller-Immerglück M. M., Schaffner W., Matthias P. Transcription factor Oct-2A contains functionally redundant activating domains and works selectively from a promoter but not from a remote enhancer position in non-lymphoid (HeLa) cells. EMBO J. 1990 May;9(5):1625–1634. doi: 10.1002/j.1460-2075.1990.tb08282.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Müller M. M., Ruppert S., Schaffner W., Matthias P. A cloned octamer transcription factor stimulates transcription from lymphoid-specific promoters in non-B cells. Nature. 1988 Dec 8;336(6199):544–551. doi: 10.1038/336544a0. [DOI] [PubMed] [Google Scholar]
  60. Nourse J., Mellentin J. D., Galili N., Wilkinson J., Stanbridge E., Smith S. D., Cleary M. L. Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor. Cell. 1990 Feb 23;60(4):535–545. doi: 10.1016/0092-8674(90)90657-z. [DOI] [PubMed] [Google Scholar]
  61. Nussenzweig M. C., Shaw A. C., Sinn E., Danner D. B., Holmes K. L., Morse H. C., 3rd, Leder P. Allelic exclusion in transgenic mice that express the membrane form of immunoglobulin mu. Science. 1987 May 15;236(4803):816–819. doi: 10.1126/science.3107126. [DOI] [PubMed] [Google Scholar]
  62. O'Hare P., Goding C. R., Haigh A. Direct combinatorial interaction between a herpes simplex virus regulatory protein and a cellular octamer-binding factor mediates specific induction of virus immediate-early gene expression. EMBO J. 1988 Dec 20;7(13):4231–4238. doi: 10.1002/j.1460-2075.1988.tb03320.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. O'Hare P., Goding C. R. Herpes simplex virus regulatory elements and the immunoglobulin octamer domain bind a common factor and are both targets for virion transactivation. Cell. 1988 Feb 12;52(3):435–445. doi: 10.1016/s0092-8674(88)80036-9. [DOI] [PubMed] [Google Scholar]
  64. Pabo C. O., Sauer R. T. Transcription factors: structural families and principles of DNA recognition. Annu Rev Biochem. 1992;61:1053–1095. doi: 10.1146/annurev.bi.61.070192.005201. [DOI] [PubMed] [Google Scholar]
  65. Palmiter R. D., Brinster R. L. Germ-line transformation of mice. Annu Rev Genet. 1986;20:465–499. doi: 10.1146/annurev.ge.20.120186.002341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Pierani A., Heguy A., Fujii H., Roeder R. G. Activation of octamer-containing promoters by either octamer-binding transcription factor 1 (OTF-1) or OTF-2 and requirement of an additional B-cell-specific component for optimal transcription of immunoglobulin promoters. Mol Cell Biol. 1990 Dec;10(12):6204–6215. doi: 10.1128/mcb.10.12.6204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Poellinger L., Yoza B. K., Roeder R. G. Functional cooperativity between protein molecules bound at two distinct sequence elements of the immunoglobulin heavy-chain promoter. Nature. 1989 Feb 9;337(6207):573–576. doi: 10.1038/337573a0. [DOI] [PubMed] [Google Scholar]
  68. Pomerantz J. L., Kristie T. M., Sharp P. A. Recognition of the surface of a homeo domain protein. Genes Dev. 1992 Nov;6(11):2047–2057. doi: 10.1101/gad.6.11.2047. [DOI] [PubMed] [Google Scholar]
  69. Prendergast G. C., Lawe D., Ziff E. B. Association of Myn, the murine homolog of max, with c-Myc stimulates methylation-sensitive DNA binding and ras cotransformation. Cell. 1991 May 3;65(3):395–407. doi: 10.1016/0092-8674(91)90457-a. [DOI] [PubMed] [Google Scholar]
  70. Rabbitts T. H. Translocations, master genes, and differences between the origins of acute and chronic leukemias. Cell. 1991 Nov 15;67(4):641–644. doi: 10.1016/0092-8674(91)90057-6. [DOI] [PubMed] [Google Scholar]
  71. Rosenfeld M. G. POU-domain transcription factors: pou-er-ful developmental regulators. Genes Dev. 1991 Jun;5(6):897–907. doi: 10.1101/gad.5.6.897. [DOI] [PubMed] [Google Scholar]
  72. 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]
  73. Scheidereit C., Cromlish J. A., Gerster T., Kawakami K., Balmaceda C. G., Currie R. A., Roeder R. G. A human lymphoid-specific transcription factor that activates immunoglobulin genes is a homoeobox protein. Nature. 1988 Dec 8;336(6199):551–557. doi: 10.1038/336551a0. [DOI] [PubMed] [Google Scholar]
  74. Schmidt E. V., Pattengale P. K., Weir L., Leder P. Transgenic mice bearing the human c-myc gene activated by an immunoglobulin enhancer: a pre-B-cell lymphoma model. Proc Natl Acad Sci U S A. 1988 Aug;85(16):6047–6051. doi: 10.1073/pnas.85.16.6047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Schreiber E., Matthias P., Müller M. M., Schaffner W. Identification of a novel lymphoid specific octamer binding protein (OTF-2B) by proteolytic clipping bandshift assay (PCBA). EMBO J. 1988 Dec 20;7(13):4221–4229. doi: 10.1002/j.1460-2075.1988.tb03319.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Schöler H. R. Octamania: the POU factors in murine development. Trends Genet. 1991 Oct;7(10):323–329. doi: 10.1016/0168-9525(91)90422-m. [DOI] [PubMed] [Google Scholar]
  77. Scott M. P., Tamkun J. W., Hartzell G. W., 3rd The structure and function of the homeodomain. Biochim Biophys Acta. 1989 Jul 28;989(1):25–48. doi: 10.1016/0304-419x(89)90033-4. [DOI] [PubMed] [Google Scholar]
  78. Sharif M., Privalsky M. L. v-erbA oncogene function in neoplasia correlates with its ability to repress retinoic acid receptor action. Cell. 1991 Sep 6;66(5):885–893. doi: 10.1016/0092-8674(91)90435-2. [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. Staudt L. M., Clerc R. G., Singh H., LeBowitz J. H., Sharp P. A., Baltimore D. Cloning of a lymphoid-specific cDNA encoding a protein binding the regulatory octamer DNA motif. Science. 1988 Jul 29;241(4865):577–580. doi: 10.1126/science.3399892. [DOI] [PubMed] [Google Scholar]
  81. Stern S., Tanaka M., Herr W. The Oct-1 homoeodomain directs formation of a multiprotein-DNA complex with the HSV transactivator VP16. Nature. 1989 Oct 19;341(6243):624–630. doi: 10.1038/341624a0. [DOI] [PubMed] [Google Scholar]
  82. Stewart T. A., Pattengale P. K., Leder P. Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes. Cell. 1984 Oct;38(3):627–637. doi: 10.1016/0092-8674(84)90257-5. [DOI] [PubMed] [Google Scholar]
  83. Stoykova A. S., Sterrer S., Erselius J. R., Hatzopoulos A. K., Gruss P. Mini-Oct and Oct-2c: two novel, functionally diverse murine Oct-2 gene products are differentially expressed in the CNS. Neuron. 1992 Mar;8(3):541–558. doi: 10.1016/0896-6273(92)90282-i. [DOI] [PubMed] [Google Scholar]
  84. Studier F. W., Rosenberg A. H., Dunn J. J., Dubendorff J. W. Use of T7 RNA polymerase to direct expression of cloned genes. Methods Enzymol. 1990;185:60–89. doi: 10.1016/0076-6879(90)85008-c. [DOI] [PubMed] [Google Scholar]
  85. Sturm R. A., Das G., Herr W. The ubiquitous octamer-binding protein Oct-1 contains a POU domain with a homeo box subdomain. Genes Dev. 1988 Dec;2(12A):1582–1599. doi: 10.1101/gad.2.12a.1582. [DOI] [PubMed] [Google Scholar]
  86. Sturm R. A., Herr W. The POU domain is a bipartite DNA-binding structure. Nature. 1988 Dec 8;336(6199):601–604. doi: 10.1038/336601a0. [DOI] [PubMed] [Google Scholar]
  87. Verrijzer C. P., Van der Vliet P. C. POU domain transcription factors. Biochim Biophys Acta. 1993 Apr 29;1173(1):1–21. doi: 10.1016/0167-4781(93)90237-8. [DOI] [PubMed] [Google Scholar]
  88. Verrijzer C. P., van Oosterhout J. A., van Weperen W. W., van der Vliet P. C. POU proteins bend DNA via the POU-specific domain. EMBO J. 1991 Oct;10(10):3007–3014. doi: 10.1002/j.1460-2075.1991.tb07851.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Vogelstein B., Kinzler K. W. The multistep nature of cancer. Trends Genet. 1993 Apr;9(4):138–141. doi: 10.1016/0168-9525(93)90209-z. [DOI] [PubMed] [Google Scholar]
  90. Weinberg R. A. Tumor suppressor genes. Science. 1991 Nov 22;254(5035):1138–1146. doi: 10.1126/science.1659741. [DOI] [PubMed] [Google Scholar]
  91. Xiong Y., Hannon G. J., Zhang H., Casso D., Kobayashi R., Beach D. p21 is a universal inhibitor of cyclin kinases. Nature. 1993 Dec 16;366(6456):701–704. doi: 10.1038/366701a0. [DOI] [PubMed] [Google Scholar]
  92. 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]
  93. 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]
  94. de Thé H., Lavau C., Marchio A., Chomienne C., Degos L., Dejean A. The PML-RAR alpha fusion mRNA generated by the t(15;17) translocation in acute promyelocytic leukemia encodes a functionally altered RAR. Cell. 1991 Aug 23;66(4):675–684. doi: 10.1016/0092-8674(91)90113-d. [DOI] [PubMed] [Google Scholar]
  95. 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 The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES