Skip to main content
NCBI home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1995 Mar;15(3):1522–1535. doi: 10.1128/mcb.15.3.1522

The PAX3-FKHR fusion protein created by the t(2;13) translocation in alveolar rhabdomyosarcomas is a more potent transcriptional activator than PAX3.

W J Fredericks 1, N Galili 1, S Mukhopadhyay 1, G Rovera 1, J Bennicelli 1, F G Barr 1, F J Rauscher 3rd 1
PMCID: PMC230376  PMID: 7862145

Abstract

Alveolar rhabdomyosarcomas are pediatric solid tumors with a hallmark cytogenetic abnormality: translocation of chromosomes 2 and 13 [t(2;13) (q35;q14)]. The genes on each chromosome involved in this translocation have been identified as the transcription factor-encoding genes PAX3 and FKHR. The NH2-terminal paired box and homeodomain DNA-binding domains of PAX3 are fused in frame to COOH-terminal regions of the chromosome 13-derived FKHR gene, a novel member of the forkhead DNA-binding domain family. To determine the role of the fusion protein in transcriptional regulation and oncogenesis, we identified the PAX3-FKHR fusion protein and characterized its function(s) as a transcription factor relative to wild-type PAX3. Antisera specific to PAX3 and FKHR were developed and used to examine PAX3 and PAX3-FKHR expression in tumor cell lines. Sequential immunoprecipitations with anti-PAX3 and anti-FKHR sera demonstrated expression of a 97-kDa PAX3-FKHR fusion protein in the t(2;13)-positive rhabdomyosarcoma Rh30 cell line and verified that a single polypeptide contains epitopes derived from each protein. The PAX3-FKHR protein was localized to the nucleus in Rh30 cells, as was wild-type PAX3, in t(2;13)-negative A673 cells. In gel shift assays using a canonical PAX binding site (e5 sequence), we found that DNA binding of PAX3-FKHR was significantly impaired relative to that of PAX3 despite the two proteins having identical PAX DNA-binding domains. However, the PAX3-FKHR fusion protein was a much more potent transcriptional activator than PAX3 as determined by transient cotransfection assays using e5-CAT reporter plasmids. The PAX3-FKHR protein may function as an oncogenic transcription factor by enhanced activation of normal PAX3 target genes.

Full Text

The Full Text of this article is available as a PDF (985.1 KB).

Selected References

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

  1. Bailly R. A., Bosselut R., Zucman J., Cormier F., Delattre O., Roussel M., Thomas G., Ghysdael J. DNA-binding and transcriptional activation properties of the EWS-FLI-1 fusion protein resulting from the t(11;22) translocation in Ewing sarcoma. Mol Cell Biol. 1994 May;14(5):3230–3241. doi: 10.1128/mcb.14.5.3230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balling R., Deutsch U., Gruss P. undulated, a mutation affecting the development of the mouse skeleton, has a point mutation in the paired box of Pax 1. Cell. 1988 Nov 4;55(3):531–535. doi: 10.1016/0092-8674(88)90039-6. [DOI] [PubMed] [Google Scholar]
  3. Barr F. G., Biegel J. A., Sellinger B., Womer R. B., Emanuel B. S. Molecular and cytogenetic analysis of chromosomal arms 2q and 13q in alveolar rhabdomyosarcoma. Genes Chromosomes Cancer. 1991 Mar;3(2):153–161. doi: 10.1002/gcc.2870030212. [DOI] [PubMed] [Google Scholar]
  4. Barr F. G., Galili N., Holick J., Biegel J. A., Rovera G., Emanuel B. S. Rearrangement of the PAX3 paired box gene in the paediatric solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993 Feb;3(2):113–117. doi: 10.1038/ng0293-113. [DOI] [PubMed] [Google Scholar]
  5. Barr F. G., Holick J., Nycum L., Biegel J. A., Emanuel B. S. Localization of the t(2;13) breakpoint of alveolar rhabdomyosarcoma on a physical map of chromosome 2. Genomics. 1992 Aug;13(4):1150–1156. doi: 10.1016/0888-7543(92)90030-v. [DOI] [PubMed] [Google Scholar]
  6. Barr F. G., Sellinger B., Emanuel B. S. Localization of the rhabdomyosarcoma t(2;13) breakpoint on a physical map of chromosome 13. Genomics. 1991 Dec;11(4):941–947. doi: 10.1016/0888-7543(91)90018-a. [DOI] [PubMed] [Google Scholar]
  7. Bartram C. R., de Klein A., Hagemeijer A., van Agthoven T., Geurts van Kessel A., Bootsma D., Grosveld G., Ferguson-Smith M. A., Davies T., Stone M. Translocation of c-ab1 oncogene correlates with the presence of a Philadelphia chromosome in chronic myelocytic leukaemia. Nature. 1983 Nov 17;306(5940):277–280. doi: 10.1038/306277a0. [DOI] [PubMed] [Google Scholar]
  8. Bober E., Franz T., Arnold H. H., Gruss P., Tremblay P. Pax-3 is required for the development of limb muscles: a possible role for the migration of dermomyotomal muscle progenitor cells. Development. 1994 Mar;120(3):603–612. doi: 10.1242/dev.120.3.603. [DOI] [PubMed] [Google Scholar]
  9. Brennan R. G. The winged-helix DNA-binding motif: another helix-turn-helix takeoff. Cell. 1993 Sep 10;74(5):773–776. doi: 10.1016/0092-8674(93)90456-z. [DOI] [PubMed] [Google Scholar]
  10. Burri M., Tromvoukis Y., Bopp D., Frigerio G., Noll M. Conservation of the paired domain in metazoans and its structure in three isolated human genes. EMBO J. 1989 Apr;8(4):1183–1190. doi: 10.1002/j.1460-2075.1989.tb03490.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Carriere C., Plaza S., Martin P., Quatannens B., Bailly M., Stehelin D., Saule S. Characterization of quail Pax-6 (Pax-QNR) proteins expressed in the neuroretina. Mol Cell Biol. 1993 Dec;13(12):7257–7266. doi: 10.1128/mcb.13.12.7257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chalepakis G., Fritsch R., Fickenscher H., Deutsch U., Goulding M., Gruss P. The molecular basis of the undulated/Pax-1 mutation. Cell. 1991 Sep 6;66(5):873–884. doi: 10.1016/0092-8674(91)90434-z. [DOI] [PubMed] [Google Scholar]
  13. Chalepakis G., Goulding M., Read A., Strachan T., Gruss P. Molecular basis of splotch and Waardenburg Pax-3 mutations. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3685–3689. doi: 10.1073/pnas.91.9.3685. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Chalepakis G., Tremblay P., Gruss P. Pax genes, mutants and molecular function. J Cell Sci Suppl. 1992;16:61–67. doi: 10.1242/jcs.1992.supplement_16.8. [DOI] [PubMed] [Google Scholar]
  15. Chalepakis G., Wijnholds J., Gruss P. Pax-3-DNA interaction: flexibility in the DNA binding and induction of DNA conformational changes by paired domains. Nucleic Acids Res. 1994 Aug 11;22(15):3131–3137. doi: 10.1093/nar/22.15.3131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Clark K. L., Halay E. D., Lai E., Burley S. K. Co-crystal structure of the HNF-3/fork head DNA-recognition motif resembles histone H5. Nature. 1993 Jul 29;364(6436):412–420. doi: 10.1038/364412a0. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Clevidence D. E., Overdier D. G., Tao W., Qian X., Pani L., Lai E., Costa R. H. Identification of nine tissue-specific transcription factors of the hepatocyte nuclear factor 3/forkhead DNA-binding-domain family. Proc Natl Acad Sci U S A. 1993 May 1;90(9):3948–3952. doi: 10.1073/pnas.90.9.3948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Crozat A., Aman P., Mandahl N., Ron D. Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma. Nature. 1993 Jun 17;363(6430):640–644. doi: 10.1038/363640a0. [DOI] [PubMed] [Google Scholar]
  20. Czerny T., Schaffner G., Busslinger M. DNA sequence recognition by Pax proteins: bipartite structure of the paired domain and its binding site. Genes Dev. 1993 Oct;7(10):2048–2061. doi: 10.1101/gad.7.10.2048. [DOI] [PubMed] [Google Scholar]
  21. Douglass E. C., Valentine M., Etcubanas E., Parham D., Webber B. L., Houghton P. J., Houghton J. A., Green A. A. A specific chromosomal abnormality in rhabdomyosarcoma. Cytogenet Cell Genet. 1987;45(3-4):148–155. doi: 10.1159/000132446. [DOI] [PubMed] [Google Scholar]
  22. Dozier C., Carrière C., Grévin D., Martin P., Quatannens B., Stéhelin D., Saule S. Structure and DNA-binding properties of Pax-QNR, a paired box- and homeobox-containing gene. Cell Growth Differ. 1993 Apr;4(4):281–289. [PubMed] [Google Scholar]
  23. Epstein D. J., Vogan K. J., Trasler D. G., Gros P. A mutation within intron 3 of the Pax-3 gene produces aberrantly spliced mRNA transcripts in the splotch (Sp) mouse mutant. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):532–536. doi: 10.1073/pnas.90.2.532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Epstein J., Cai J., Glaser T., Jepeal L., Maas R. Identification of a Pax paired domain recognition sequence and evidence for DNA-dependent conformational changes. J Biol Chem. 1994 Mar 18;269(11):8355–8361. [PubMed] [Google Scholar]
  25. Evans H. J. Molecular genetic aspects of human cancers: the 1993 Frank Rose Lecture. Br J Cancer. 1993 Dec;68(6):1051–1060. doi: 10.1038/bjc.1993.482. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Foy C., Newton V., Wellesley D., Harris R., Read A. P. Assignment of the locus for Waardenburg syndrome type I to human chromosome 2q37 and possible homology to the Splotch mouse. Am J Hum Genet. 1990 Jun;46(6):1017–1023. [PMC free article] [PubMed] [Google Scholar]
  27. Galili N., Davis R. J., Fredericks W. J., Mukhopadhyay S., Rauscher F. J., 3rd, Emanuel B. S., Rovera G., Barr F. G. Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma. Nat Genet. 1993 Nov;5(3):230–235. doi: 10.1038/ng1193-230. [DOI] [PubMed] [Google Scholar]
  28. Gehring W. J. Homeo boxes in the study of development. Science. 1987 Jun 5;236(4806):1245–1252. doi: 10.1126/science.2884726. [DOI] [PubMed] [Google Scholar]
  29. Goulding M. D., Chalepakis G., Deutsch U., Erselius J. R., Gruss P. Pax-3, a novel murine DNA binding protein expressed during early neurogenesis. EMBO J. 1991 May;10(5):1135–1147. doi: 10.1002/j.1460-2075.1991.tb08054.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Goulding M. D., Lumsden A., Gruss P. Signals from the notochord and floor plate regulate the region-specific expression of two Pax genes in the developing spinal cord. Development. 1993 Mar;117(3):1001–1016. doi: 10.1242/dev.117.3.1001. [DOI] [PubMed] [Google Scholar]
  31. Goulding M., Lumsden A., Paquette A. J. Regulation of Pax-3 expression in the dermomyotome and its role in muscle development. Development. 1994 Apr;120(4):957–971. doi: 10.1242/dev.120.4.957. [DOI] [PubMed] [Google Scholar]
  32. Goulding M., Sterrer S., Fleming J., Balling R., Nadeau J., Moore K. J., Brown S. D., Steel K. P., Gruss P. Analysis of the Pax-3 gene in the mouse mutant splotch. Genomics. 1993 Aug;17(2):355–363. doi: 10.1006/geno.1993.1332. [DOI] [PubMed] [Google Scholar]
  33. Grignani F., Fagioli M., Alcalay M., Longo L., Pandolfi P. P., Donti E., Biondi A., Lo Coco F., Grignani F., Pelicci P. G. Acute promyelocytic leukemia: from genetics to treatment. Blood. 1994 Jan 1;83(1):10–25. [PubMed] [Google Scholar]
  34. Gruss P., Walther C. Pax in development. Cell. 1992 May 29;69(5):719–722. doi: 10.1016/0092-8674(92)90281-g. [DOI] [PubMed] [Google Scholar]
  35. Han K., Levine M. S., Manley J. L. Synergistic activation and repression of transcription by Drosophila homeobox proteins. Cell. 1989 Feb 24;56(4):573–583. doi: 10.1016/0092-8674(89)90580-1. [DOI] [PubMed] [Google Scholar]
  36. Hayashi S., Scott M. P. What determines the specificity of action of Drosophila homeodomain proteins? Cell. 1990 Nov 30;63(5):883–894. doi: 10.1016/0092-8674(90)90492-w. [DOI] [PubMed] [Google Scholar]
  37. Hill R. E., Favor J., Hogan B. L., Ton C. C., Saunders G. F., Hanson I. M., Prosser J., Jordan T., Hastie N. D., van Heyningen V. Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature. 1991 Dec 19;354(6354):522–525. doi: 10.1038/354522a0. [DOI] [PubMed] [Google Scholar]
  38. Hill R. E., Hanson I. M. Molecular genetics of the Pax gene family. Curr Opin Cell Biol. 1992 Dec;4(6):967–972. doi: 10.1016/0955-0674(92)90126-w. [DOI] [PubMed] [Google Scholar]
  39. Hoey T., Levine M. Divergent homeo box proteins recognize similar DNA sequences in Drosophila. Nature. 1988 Apr 28;332(6167):858–861. doi: 10.1038/332858a0. [DOI] [PubMed] [Google Scholar]
  40. Hoey T., Warrior R., Manak J., Levine M. DNA-binding activities of the Drosophila melanogaster even-skipped protein are mediated by its homeo domain and influenced by protein context. Mol Cell Biol. 1988 Nov;8(11):4598–4607. doi: 10.1128/mcb.8.11.4598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Hromas R., Moore J., Johnston T., Socha C., Klemsz M. Drosophila forkhead homologues are expressed in a lineage-restricted manner in human hematopoietic cells. Blood. 1993 Jun 1;81(11):2854–2859. [PubMed] [Google Scholar]
  42. Hunger S. P., Ohyashiki K., Toyama K., Cleary M. L. Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia. Genes Dev. 1992 Sep;6(9):1608–1620. doi: 10.1101/gad.6.9.1608. [DOI] [PubMed] [Google Scholar]
  43. Inaba T., Shapiro L. H., Funabiki T., Sinclair A. E., Jones B. G., Ashmun R. A., Look A. T. DNA-binding specificity and trans-activating potential of the leukemia-associated E2A-hepatic leukemia factor fusion protein. Mol Cell Biol. 1994 May;14(5):3403–3413. doi: 10.1128/mcb.14.5.3403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Jordan T., Hanson I., Zaletayev D., Hodgson S., Prosser J., Seawright A., Hastie N., van Heyningen V. The human PAX6 gene is mutated in two patients with aniridia. Nat Genet. 1992 Aug;1(5):328–332. doi: 10.1038/ng0892-328. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. 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]
  47. Lassar A. B., Davis R. L., Wright W. E., Kadesch T., Murre C., Voronova A., Baltimore D., Weintraub H. Functional activity of myogenic HLH proteins requires hetero-oligomerization with E12/E47-like proteins in vivo. Cell. 1991 Jul 26;66(2):305–315. doi: 10.1016/0092-8674(91)90620-e. [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. 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]
  50. Madden S. L., Cook D. M., Rauscher F. J., 3rd A structure-function analysis of transcriptional repression mediated by the WT1, Wilms' tumor suppressor protein. Oncogene. 1993 Jul;8(7):1713–1720. [PubMed] [Google Scholar]
  51. 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]
  52. May W. A., Lessnick S. L., Braun B. S., Klemsz M., Lewis B. C., Lunsford L. B., Hromas R., Denny C. T. The Ewing's sarcoma EWS/FLI-1 fusion gene encodes a more potent transcriptional activator and is a more powerful transforming gene than FLI-1. Mol Cell Biol. 1993 Dec;13(12):7393–7398. doi: 10.1128/mcb.13.12.7393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Mitchell P. J., Tjian R. Transcriptional regulation in mammalian cells by sequence-specific DNA binding proteins. Science. 1989 Jul 28;245(4916):371–378. doi: 10.1126/science.2667136. [DOI] [PubMed] [Google Scholar]
  54. Moase C. E., Trasler D. G. N-CAM alterations in splotch neural tube defect mouse embryos. Development. 1991 Nov;113(3):1049–1058. doi: 10.1242/dev.113.3.1049. [DOI] [PubMed] [Google Scholar]
  55. Morell R., Friedman T. B., Moeljopawiro S., Hartono, Soewito, Asher J. H., Jr A frameshift mutation in the HuP2 paired domain of the probable human homolog of murine Pax-3 is responsible for Waardenburg syndrome type 1 in an Indonesian family. Hum Mol Genet. 1992 Jul;1(4):243–247. doi: 10.1093/hmg/1.4.243. [DOI] [PubMed] [Google Scholar]
  56. Morris J. F., Madden S. L., Tournay O. E., Cook D. M., Sukhatme V. P., Rauscher F. J., 3rd Characterization of the zinc finger protein encoded by the WT1 Wilms' tumor locus. Oncogene. 1991 Dec;6(12):2339–2348. [PubMed] [Google Scholar]
  57. 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]
  58. Overdier D. G., Porcella A., Costa R. H. The DNA-binding specificity of the hepatocyte nuclear factor 3/forkhead domain is influenced by amino-acid residues adjacent to the recognition helix. Mol Cell Biol. 1994 Apr;14(4):2755–2766. doi: 10.1128/mcb.14.4.2755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Pierpont J. W., Erickson R. P. Facts on PAX. Am J Hum Genet. 1993 Mar;52(3):451–454. [PMC free article] [PubMed] [Google Scholar]
  60. 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]
  61. Rabbitts T. H., Forster A., Larson R., Nathan P. Fusion of the dominant negative transcription regulator CHOP with a novel gene FUS by translocation t(12;16) in malignant liposarcoma. Nat Genet. 1993 Jun;4(2):175–180. doi: 10.1038/ng0693-175. [DOI] [PubMed] [Google Scholar]
  62. 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]
  63. Rauscher F. J., 3rd, Cohen D. R., Curran T., Bos T. J., Vogt P. K., Bohmann D., Tjian R., Franza B. R., Jr Fos-associated protein p39 is the product of the jun proto-oncogene. Science. 1988 May 20;240(4855):1010–1016. doi: 10.1126/science.3130660. [DOI] [PubMed] [Google Scholar]
  64. Rauscher F. J., 3rd, Voulalas P. J., Franza B. R., Jr, Curran T. Fos and Jun bind cooperatively to the AP-1 site: reconstitution in vitro. Genes Dev. 1988 Dec;2(12B):1687–1699. doi: 10.1101/gad.2.12b.1687. [DOI] [PubMed] [Google Scholar]
  65. Sasaki H., Hogan B. L. Differential expression of multiple fork head related genes during gastrulation and axial pattern formation in the mouse embryo. Development. 1993 May;118(1):47–59. doi: 10.1242/dev.118.1.47. [DOI] [PubMed] [Google Scholar]
  66. Schöler H. R., Hatzopoulos A. K., Balling R., Suzuki N., Gruss P. A family of octamer-specific proteins present during mouse embryogenesis: evidence for germline-specific expression of an Oct factor. EMBO J. 1989 Sep;8(9):2543–2550. doi: 10.1002/j.1460-2075.1989.tb08392.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Shapiro D. N., Sublett J. E., Li B., Downing J. R., Naeve C. W. Fusion of PAX3 to a member of the forkhead family of transcription factors in human alveolar rhabdomyosarcoma. Cancer Res. 1993 Nov 1;53(21):5108–5112. [PubMed] [Google Scholar]
  68. Shapiro D. N., Valentine M. B., Sublett J. E., Sinclair A. E., Tereba A. M., Scheffer H., Buys C. H., Look A. T. Chromosomal sublocalization of the 2;13 translocation breakpoint in alveolar rhabdomyosarcoma. Genes Chromosomes Cancer. 1992 Apr;4(3):241–249. doi: 10.1002/gcc.2870040309. [DOI] [PubMed] [Google Scholar]
  69. Solomon E., Borrow J., Goddard A. D. Chromosome aberrations and cancer. Science. 1991 Nov 22;254(5035):1153–1160. doi: 10.1126/science.1957167. [DOI] [PubMed] [Google Scholar]
  70. Stapleton P., Weith A., Urbánek P., Kozmik Z., Busslinger M. Chromosomal localization of seven PAX genes and cloning of a novel family member, PAX-9. Nat Genet. 1993 Apr;3(4):292–298. doi: 10.1038/ng0493-292. [DOI] [PubMed] [Google Scholar]
  71. Tassabehji M., Read A. P., Newton V. E., Patton M., Gruss P., Harris R., Strachan T. Mutations in the PAX3 gene causing Waardenburg syndrome type 1 and type 2. Nat Genet. 1993 Jan;3(1):26–30. doi: 10.1038/ng0193-26. [DOI] [PubMed] [Google Scholar]
  72. Thomsen D. R., Stenberg R. M., Goins W. F., Stinski M. F. Promoter-regulatory region of the major immediate early gene of human cytomegalovirus. Proc Natl Acad Sci U S A. 1984 Feb;81(3):659–663. doi: 10.1073/pnas.81.3.659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Ton C. C., Hirvonen H., Miwa H., Weil M. M., Monaghan P., Jordan T., van Heyningen V., Hastie N. D., Meijers-Heijboer H., Drechsler M. Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell. 1991 Dec 20;67(6):1059–1074. doi: 10.1016/0092-8674(91)90284-6. [DOI] [PubMed] [Google Scholar]
  74. Ton C. C., Miwa H., Saunders G. F. Small eye (Sey): cloning and characterization of the murine homolog of the human aniridia gene. Genomics. 1992 Jun;13(2):251–256. doi: 10.1016/0888-7543(92)90239-o. [DOI] [PubMed] [Google Scholar]
  75. Treisman J., Gönczy P., Vashishtha M., Harris E., Desplan C. A single amino acid can determine the DNA binding specificity of homeodomain proteins. Cell. 1989 Nov 3;59(3):553–562. doi: 10.1016/0092-8674(89)90038-x. [DOI] [PubMed] [Google Scholar]
  76. Treisman J., Harris E., Desplan C. The paired box encodes a second DNA-binding domain in the paired homeo domain protein. Genes Dev. 1991 Apr;5(4):594–604. doi: 10.1101/gad.5.4.594. [DOI] [PubMed] [Google Scholar]
  77. Treisman J., Harris E., Wilson D., Desplan C. The homeodomain: a new face for the helix-turn-helix? Bioessays. 1992 Mar;14(3):145–150. doi: 10.1002/bies.950140302. [DOI] [PubMed] [Google Scholar]
  78. Turc-Carel C., Lizard-Nacol S., Justrabo E., Favrot M., Philip T., Tabone E. Consistent chromosomal translocation in alveolar rhabdomyosarcoma. Cancer Genet Cytogenet. 1986 Jan 15;19(3-4):361–362. doi: 10.1016/0165-4608(86)90069-5. [DOI] [PubMed] [Google Scholar]
  79. Van Dijk M. A., Voorhoeve P. M., Murre C. Pbx1 is converted into a transcriptional activator upon acquiring the N-terminal region of E2A in pre-B-cell acute lymphoblastoid leukemia. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6061–6065. doi: 10.1073/pnas.90.13.6061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Weigel D., Jäckle H. The fork head domain: a novel DNA binding motif of eukaryotic transcription factors? Cell. 1990 Nov 2;63(3):455–456. doi: 10.1016/0092-8674(90)90439-l. [DOI] [PubMed] [Google Scholar]
  81. Williams B. A., Ordahl C. P. Pax-3 expression in segmental mesoderm marks early stages in myogenic cell specification. Development. 1994 Apr;120(4):785–796. doi: 10.1242/dev.120.4.785. [DOI] [PubMed] [Google Scholar]
  82. Wilson D., Sheng G., Lecuit T., Dostatni N., Desplan C. Cooperative dimerization of paired class homeo domains on DNA. Genes Dev. 1993 Nov;7(11):2120–2134. doi: 10.1101/gad.7.11.2120. [DOI] [PubMed] [Google Scholar]
  83. Zucman J., Delattre O., Desmaze C., Epstein A. L., Stenman G., Speleman F., Fletchers C. D., Aurias A., Thomas G. EWS and ATF-1 gene fusion induced by t(12;22) translocation in malignant melanoma of soft parts. Nat Genet. 1993 Aug;4(4):341–345. doi: 10.1038/ng0893-341. [DOI] [PubMed] [Google Scholar]
  84. de Klein A., van Kessel A. G., Grosveld G., Bartram C. R., Hagemeijer A., Bootsma D., Spurr N. K., Heisterkamp N., Groffen J., Stephenson J. R. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature. 1982 Dec 23;300(5894):765–767. doi: 10.1038/300765a0. [DOI] [PubMed] [Google Scholar]
  85. 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]

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

RESOURCES