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. 1994 May 24;91(11):4915–4919. doi: 10.1073/pnas.91.11.4915

LR1 regulates c-myc transcription in B-cell lymphomas.

A Brys 1, N Maizels 1
PMCID: PMC43900  PMID: 8197157

Abstract

LR1 is a 106-kDa sequence-specific DNA-binding protein first identified as a potential regulator of immunoglobulin class switch recombination in B lymphocytes. Here we report that LR1 binds to a site 310 nt upstream of the human c-myc P1 promoter. Mutation of this site decreases reporter gene expression 5.5-fold in the Burkitt lymphoma line Raji and 3.8-fold in the lymphoma line BJAB. These experiments show that LR1 can function as a transcription factor and identify it as a cell type-specific activator of c-myc expression. There are multiple matches to the LR1 recognition consensus at the immunoglobulin heavy-chain locus and at c-myc, which further suggests that LR1 may play a dual role, facilitating c-myc translocation as well as regulating c-myc transcription.

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Selected References

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

  1. Ahn J. K., Gavin B. J., Kumar G., Ward D. C. Transcriptional analysis of minute virus of mice P4 promoter mutants. J Virol. 1989 Dec;63(12):5425–5439. doi: 10.1128/jvi.63.12.5425-5439.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barberis A., Widenhorn K., Vitelli L., Busslinger M. A novel B-cell lineage-specific transcription factor present at early but not late stages of differentiation. Genes Dev. 1990 May;4(5):849–859. doi: 10.1101/gad.4.5.849. [DOI] [PubMed] [Google Scholar]
  3. Cory S. Activation of cellular oncogenes in hemopoietic cells by chromosome translocation. Adv Cancer Res. 1986;47:189–234. doi: 10.1016/s0065-230x(08)60200-6. [DOI] [PubMed] [Google Scholar]
  4. Croce C. M., Nowell P. C. Molecular genetics of human B cell neoplasia. Adv Immunol. 1986;38:245–274. doi: 10.1016/s0065-2776(08)60008-5. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Dunnick W., Hertz G. Z., Scappino L., Gritzmacher C. DNA sequences at immunoglobulin switch region recombination sites. Nucleic Acids Res. 1993 Feb 11;21(3):365–372. doi: 10.1093/nar/21.3.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Duyao M. P., Buckler A. J., Sonenshein G. E. Interaction of an NF-kappa B-like factor with a site upstream of the c-myc promoter. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4727–4731. doi: 10.1073/pnas.87.12.4727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Friedman D. I. Integration host factor: a protein for all reasons. Cell. 1988 Nov 18;55(4):545–554. doi: 10.1016/0092-8674(88)90213-9. [DOI] [PubMed] [Google Scholar]
  9. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Haluska F. G., Tsujimoto Y., Croce C. M. Oncogene activation by chromosome translocation in human malignancy. Annu Rev Genet. 1987;21:321–345. doi: 10.1146/annurev.ge.21.120187.001541. [DOI] [PubMed] [Google Scholar]
  11. Hay N., Bishop J. M., Levens D. Regulatory elements that modulate expression of human c-myc. Genes Dev. 1987 Sep;1(7):659–671. doi: 10.1101/gad.1.7.659. [DOI] [PubMed] [Google Scholar]
  12. Hay N., Takimoto M., Bishop J. M. A FOS protein is present in a complex that binds a negative regulator of MYC. Genes Dev. 1989 Mar;3(3):293–303. doi: 10.1101/gad.3.3.293. [DOI] [PubMed] [Google Scholar]
  13. Joos S., Falk M. H., Lichter P., Haluska F. G., Henglein B., Lenoir G. M., Bornkamm G. W. Variable breakpoints in Burkitt lymphoma cells with chromosomal t(8;14) translocation separate c-myc and the IgH locus up to several hundred kb. Hum Mol Genet. 1992 Nov;1(8):625–632. doi: 10.1093/hmg/1.8.625. [DOI] [PubMed] [Google Scholar]
  14. Kakkis E., Calame K. A plasmacytoma-specific factor binds the c-myc promoter region. Proc Natl Acad Sci U S A. 1987 Oct;84(20):7031–7035. doi: 10.1073/pnas.84.20.7031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kakkis E., Riggs K. J., Gillespie W., Calame K. A transcriptional repressor of c-myc. Nature. 1989 Jun 29;339(6227):718–721. doi: 10.1038/339718a0. [DOI] [PubMed] [Google Scholar]
  16. Kelly K., Siebenlist U. The regulation and expression of c-myc in normal and malignant cells. Annu Rev Immunol. 1986;4:317–338. doi: 10.1146/annurev.iy.04.040186.001533. [DOI] [PubMed] [Google Scholar]
  17. Lenardo M., Pierce J. W., Baltimore D. Protein-binding sites in Ig gene enhancers determine transcriptional activity and inducibility. Science. 1987 Jun 19;236(4808):1573–1577. doi: 10.1126/science.3109035. [DOI] [PubMed] [Google Scholar]
  18. Magrath I. The pathogenesis of Burkitt's lymphoma. Adv Cancer Res. 1990;55:133–270. doi: 10.1016/s0065-230x(08)60470-4. [DOI] [PubMed] [Google Scholar]
  19. Pascal E., Tjian R. Different activation domains of Sp1 govern formation of multimers and mediate transcriptional synergism. Genes Dev. 1991 Sep;5(9):1646–1656. doi: 10.1101/gad.5.9.1646. [DOI] [PubMed] [Google Scholar]
  20. Pelicci P. G., Knowles D. M., 2nd, Magrath I., Dalla-Favera R. Chromosomal breakpoints and structural alterations of the c-myc locus differ in endemic and sporadic forms of Burkitt lymphoma. Proc Natl Acad Sci U S A. 1986 May;83(9):2984–2988. doi: 10.1073/pnas.83.9.2984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Postel E. H., Mango S. E., Flint S. J. A nuclease-hypersensitive element of the human c-myc promoter interacts with a transcription initiation factor. Mol Cell Biol. 1989 Nov;9(11):5123–5133. doi: 10.1128/mcb.9.11.5123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Richman A., Hayday A. Normal expression of a rearranged and mutated c-myc oncogene after transfection into fibroblasts. Science. 1989 Oct 27;246(4929):494–497. doi: 10.1126/science.2683072. [DOI] [PubMed] [Google Scholar]
  23. Riggs K. J., Merrell K. T., Wilson G., Calame K. Common factor 1 is a transcriptional activator which binds in the c-myc promoter, the skeletal alpha-actin promoter, and the immunoglobulin heavy-chain enhancer. Mol Cell Biol. 1991 Mar;11(3):1765–1769. doi: 10.1128/mcb.11.3.1765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Salvo J. J., Grindley N. D. The gamma delta resolvase bends the res site into a recombinogenic complex. EMBO J. 1988 Nov;7(11):3609–3616. doi: 10.1002/j.1460-2075.1988.tb03239.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Spandidos D. A., Zoumpourlis V., Lang J. C. Cis-platin responsive sequences in the human c-myc promoter. Anticancer Res. 1991 May-Jun;11(3):1339–1342. [PubMed] [Google Scholar]
  26. Spencer C. A., Groudine M. Control of c-myc regulation in normal and neoplastic cells. Adv Cancer Res. 1991;56:1–48. doi: 10.1016/s0065-230x(08)60476-5. [DOI] [PubMed] [Google Scholar]
  27. Spencer C. A., LeStrange R. C., Novak U., Hayward W. S., Groudine M. The block to transcription elongation is promoter dependent in normal and Burkitt's lymphoma c-myc alleles. Genes Dev. 1990 Jan;4(1):75–88. doi: 10.1101/gad.4.1.75. [DOI] [PubMed] [Google Scholar]
  28. Takimoto M., Quinn J. P., Farina A. R., Staudt L. M., Levens D. fos/jun and octamer-binding protein interact with a common site in a negative element of the human c-myc gene. J Biol Chem. 1989 May 25;264(15):8992–8999. [PubMed] [Google Scholar]
  29. Thalmeier K., Synovzik H., Mertz R., Winnacker E. L., Lipp M. Nuclear factor E2F mediates basic transcription and trans-activation by E1a of the human MYC promoter. Genes Dev. 1989 Apr;3(4):527–536. doi: 10.1101/gad.3.4.527. [DOI] [PubMed] [Google Scholar]
  30. Waldmann T. A. The arrangement of immunoglobulin and T cell receptor genes in human lymphoproliferative disorders. Adv Immunol. 1987;40:247–321. doi: 10.1016/s0065-2776(08)60241-2. [DOI] [PubMed] [Google Scholar]
  31. Williams M., Brys A., Weiner A. M., Maizels N. A rapid method for determining the molecular weight of a protein bound to nucleic acid in a mobility shift assay. Nucleic Acids Res. 1992 Sep 25;20(18):4935–4936. doi: 10.1093/nar/20.18.4935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Williams M., Hanakahi L. A., Maizels N. Purification and properties of LR1, an inducible DNA binding protein from mammalian B lymphocytes. J Biol Chem. 1993 Jun 25;268(18):13731–13737. [PubMed] [Google Scholar]
  33. Williams M., Maizels N. LR1, a lipopolysaccharide-responsive factor with binding sites in the immunoglobulin switch regions and heavy-chain enhancer. Genes Dev. 1991 Dec;5(12A):2353–2361. doi: 10.1101/gad.5.12a.2353. [DOI] [PubMed] [Google Scholar]

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