Role of the PU.1 transcription factor in controlling differentiation of Friend erythroleukemia cells (original) (raw)

Abstract

Both viral and cellular genes have been directly implicated in pathogenesis of Friend viral erythroleukemia. The virus-encoded gp55 glycoprotein binds to erythropoietin receptors to cause mitogenesis and differentiation of erythroblasts. However, if the provirus integrates adjacent to the gene for the PU.1 transcription factor, the cell loses its commitment to terminally differentiate and becomes immortal, as indicated by its transplantability and by its potential for indefinite growth in culture (C. Spiro, B. Gliniak, and D. Kabat, J. Virol. 63:4434-4437, 1989; R. Paul, S. Schuetze, S. L. Kozak, and D. Kabat, J. Virol. 65:464-467, 1991). To test the implications of these results, we produced polyclonal antiserum to bacterially synthesized PU.1, and we used it to analyze PU.1 expression throughout leukemic progression and during chemically induced differentiation of Friend erythroleukemia (F-MEL) cell lines. This antiserum identified three electrophoretically distinct PU.1 components in extracts of F-MEL cells and demonstrated their nuclear localization. Although PU.1 proteins are abundant in F-MEL cells, they are absent or present in only trace amounts in normal erythroblasts or in differentiating erythroblasts from the preleukemic stage of Friend disease. Furthermore, chemicals (dimethyl sulfoxide or N,N'-hexamethylenebisacetamide) that overcome the blocked differentiation of F-MEL cells induce rapid declines of PU.1 mRNA and PU.1 proteins. The elimination of PU.1 proteins coincides with recommitment to the program of erythroid differentiation and with loss of immortality. These results support the hypothesis that PU.1 interferes with the commitment of erythroblasts to differentiate and that chemicals that reduce PU.1 expression reinstate the erythropoietic program.

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Selected References

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  1. Ben-David Y., Bernstein A. Friend virus-induced erythroleukemia and the multistage nature of cancer. Cell. 1991 Sep 6;66(5):831–834. doi: 10.1016/0092-8674(91)90428-2. [DOI] [PubMed] [Google Scholar]
  2. Ben-David Y., Giddens E. B., Letwin K., Bernstein A. Erythroleukemia induction by Friend murine leukemia virus: insertional activation of a new member of the ets gene family, Fli-1, closely linked to c-ets-1. Genes Dev. 1991 Jun;5(6):908–918. doi: 10.1101/gad.5.6.908. [DOI] [PubMed] [Google Scholar]
  3. Bestwick R. K., Kozak S. L., Kabat D. Overcoming interference to retroviral superinfection results in amplified expression and transmission of cloned genes. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5404–5408. doi: 10.1073/pnas.85.15.5404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bosselut R., Duvall J. F., Gégonne A., Bailly M., Hémar A., Brady J., Ghysdael J. The product of the c-ets-1 proto-oncogene and the related Ets2 protein act as transcriptional activators of the long terminal repeat of human T cell leukemia virus HTLV-1. EMBO J. 1990 Oct;9(10):3137–3144. doi: 10.1002/j.1460-2075.1990.tb07511.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Casadevall N., Lacombe C., Muller O., Gisselbrecht S., Mayeux P. Multimeric structure of the membrane erythropoietin receptor of murine erythroleukemia cells (Friend cells). Cross-linking of erythropoietin with the spleen focus-forming virus envelope protein. J Biol Chem. 1991 Aug 25;266(24):16015–16020. [PubMed] [Google Scholar]
  6. Chen Z., Banks J., Rifkind R. A., Marks P. A. Inducer-mediated commitment of murine erythroleukemia cells to differentiation: a multistep process. Proc Natl Acad Sci U S A. 1982 Jan;79(2):471–475. doi: 10.1073/pnas.79.2.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  8. Chow V., Ben-David Y., Bernstein A., Benchimol S., Mowat M. Multistage Friend erythroleukemia: independent origin of tumor clones with normal or rearranged p53 cellular oncogenes. J Virol. 1987 Sep;61(9):2777–2781. doi: 10.1128/jvi.61.9.2777-2781.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Coppola J. A., Cole M. D. Constitutive c-myc oncogene expression blocks mouse erythroleukaemia cell differentiation but not commitment. Nature. 1986 Apr 24;320(6064):760–763. doi: 10.1038/320760a0. [DOI] [PubMed] [Google Scholar]
  10. Davis L. I., Blobel G. Nuclear pore complex contains a family of glycoproteins that includes p62: glycosylation through a previously unidentified cellular pathway. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7552–7556. doi: 10.1073/pnas.84.21.7552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dmitrovsky E., Kuehl W. M., Hollis G. F., Kirsch I. R., Bender T. P., Segal S. Expression of a transfected human c-myc oncogene inhibits differentiation of a mouse erythroleukaemia cell line. Nature. 1986 Aug 21;322(6081):748–750. doi: 10.1038/322748a0. [DOI] [PubMed] [Google Scholar]
  12. Friend C., Scher W., Holland J. G., Sato T. Hemoglobin synthesis in murine virus-induced leukemic cells in vitro: stimulation of erythroid differentiation by dimethyl sulfoxide. Proc Natl Acad Sci U S A. 1971 Feb;68(2):378–382. doi: 10.1073/pnas.68.2.378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fujiwara S., Fisher R. J., Bhat N. K., Diaz de la Espina S. M., Papas T. S. A short-lived nuclear phosphoprotein encoded by the human ets-2 proto-oncogene is stabilized by activation of protein kinase C. Mol Cell Biol. 1988 Nov;8(11):4700–4706. doi: 10.1128/mcb.8.11.4700. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gliniak B. C., Kabat D. Leukemogenic membrane glycoprotein encoded by Friend spleen focus-forming virus: transport to cell surfaces and shedding are controlled by disulfide-bonded dimerization and by cleavage of a hydrophobic membrane anchor. J Virol. 1989 Sep;63(9):3561–3568. doi: 10.1128/jvi.63.9.3561-3568.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Golay J., Introna M., Graf T. A single point mutation in the v-ets oncogene affects both erythroid and myelomonocytic cell differentiation. Cell. 1988 Dec 23;55(6):1147–1158. doi: 10.1016/0092-8674(88)90259-0. [DOI] [PubMed] [Google Scholar]
  16. Gunther C. V., Nye J. A., Bryner R. S., Graves B. J. Sequence-specific DNA binding of the proto-oncoprotein ets-1 defines a transcriptional activator sequence within the long terminal repeat of the Moloney murine sarcoma virus. Genes Dev. 1990 Apr;4(4):667–679. doi: 10.1101/gad.4.4.667. [DOI] [PubMed] [Google Scholar]
  17. Gusella J., Geller R., Clarke B., Weeks V., Housman D. Commitment to erythroid differentiation by friend erythroleukemia cells: a stochastic analysis. Cell. 1976 Oct;9(2):221–229. doi: 10.1016/0092-8674(76)90113-6. [DOI] [PubMed] [Google Scholar]
  18. Hara H., Ogawa M. Erthropoietic precursors in mice with phenylhydrazine-induced anemia. Am J Hematol. 1976;1(4):453–458. doi: 10.1002/ajh.2830010410. [DOI] [PubMed] [Google Scholar]
  19. Hoatlin M. E., Kozak S. L., Lilly F., Chakraborti A., Kozak C. A., Kabat D. Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9985–9989. doi: 10.1073/pnas.87.24.9985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hofer E., Darnell J. E., Jr The primary transcription unit of the mouse beta-major globin gene. Cell. 1981 Feb;23(2):585–593. doi: 10.1016/0092-8674(81)90154-9. [DOI] [PubMed] [Google Scholar]
  21. Jackson S. P., Tjian R. O-glycosylation of eukaryotic transcription factors: implications for mechanisms of transcriptional regulation. Cell. 1988 Oct 7;55(1):125–133. doi: 10.1016/0092-8674(88)90015-3. [DOI] [PubMed] [Google Scholar]
  22. Kabat D. Molecular biology of Friend viral erythroleukemia. Curr Top Microbiol Immunol. 1989;148:1–42. doi: 10.1007/978-3-642-74700-7_1. [DOI] [PubMed] [Google Scholar]
  23. Karim F. D., Urness L. D., Thummel C. S., Klemsz M. J., McKercher S. R., Celada A., Van Beveren C., Maki R. A., Gunther C. V., Nye J. A. The ETS-domain: a new DNA-binding motif that recognizes a purine-rich core DNA sequence. Genes Dev. 1990 Sep;4(9):1451–1453. doi: 10.1101/gad.4.9.1451. [DOI] [PubMed] [Google Scholar]
  24. Kirsch I. R., Bertness V., Silver J., Hollis G. F. Regulated expression of the c-myb and c-myc oncogenes during erythroid differentiation. J Cell Biochem. 1986;32(1):11–21. doi: 10.1002/jcb.240320103. [DOI] [PubMed] [Google Scholar]
  25. Klempnauer K. H., Gonda T. J., Bishop J. M. Nucleotide sequence of the retroviral leukemia gene v-myb and its cellular progenitor c-myb: the architecture of a transduced oncogene. Cell. 1982 Dec;31(2 Pt 1):453–463. doi: 10.1016/0092-8674(82)90138-6. [DOI] [PubMed] [Google Scholar]
  26. Klemsz M. J., McKercher S. R., Celada A., Van Beveren C., Maki R. A. The macrophage and B cell-specific transcription factor PU.1 is related to the ets oncogene. Cell. 1990 Apr 6;61(1):113–124. doi: 10.1016/0092-8674(90)90219-5. [DOI] [PubMed] [Google Scholar]
  27. Kozak S. L., Kabat D. Ping-pong amplification of a retroviral vector achieves high-level gene expression: human growth hormone production. J Virol. 1990 Jul;64(7):3500–3508. doi: 10.1128/jvi.64.7.3500-3508.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kume T. U., Takada S., Obinata M. Probability that the commitment of murine erythroleukemia cell differentiation is determined by the c-myc level. J Mol Biol. 1988 Aug 20;202(4):779–786. doi: 10.1016/0022-2836(88)90558-x. [DOI] [PubMed] [Google Scholar]
  29. Lachman H. M., Skoultchi A. I. Expression of c-myc changes during differentiation of mouse erythroleukaemia cells. Nature. 1984 Aug 16;310(5978):592–594. doi: 10.1038/310592a0. [DOI] [PubMed] [Google Scholar]
  30. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  31. Li J. P., D'Andrea A. D., Lodish H. F., Baltimore D. Activation of cell growth by binding of Friend spleen focus-forming virus gp55 glycoprotein to the erythropoietin receptor. Nature. 1990 Feb 22;343(6260):762–764. doi: 10.1038/343762a0. [DOI] [PubMed] [Google Scholar]
  32. Mann R., Mulligan R. C., Baltimore D. Construction of a retrovirus packaging mutant and its use to produce helper-free defective retrovirus. Cell. 1983 May;33(1):153–159. doi: 10.1016/0092-8674(83)90344-6. [DOI] [PubMed] [Google Scholar]
  33. Marks P. A., Rifkind R. A. Erythroleukemic differentiation. Annu Rev Biochem. 1978;47:419–448. doi: 10.1146/annurev.bi.47.070178.002223. [DOI] [PubMed] [Google Scholar]
  34. McClinton D., Stafford J., Brents L., Bender T. P., Kuehl W. M. Differentiation of mouse erythroleukemia cells is blocked by late up-regulation of a c-myb transgene. Mol Cell Biol. 1990 Feb;10(2):705–710. doi: 10.1128/mcb.10.2.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Miller A. D., Law M. F., Verma I. M. Generation of helper-free amphotropic retroviruses that transduce a dominant-acting, methotrexate-resistant dihydrofolate reductase gene. Mol Cell Biol. 1985 Mar;5(3):431–437. doi: 10.1128/mcb.5.3.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Moreau-Gachelin F., Ray D., Mattei M. G., Tambourin P., Tavitian A. The putative oncogene Spi-1: murine chromosomal localization and transcriptional activation in murine acute erythroleukemias. Oncogene. 1989 Dec;4(12):1449–1456. [PubMed] [Google Scholar]
  37. Moreau-Gachelin F., Ray D., de Both N. J., van der Feltz M. J., Tambourin P., Tavitian A. Spi-1 oncogene activation in Rauscher and Friend murine virus-induced acute erythroleukemias. Leukemia. 1990 Jan;4(1):20–23. [PubMed] [Google Scholar]
  38. Moreau-Gachelin F., Tavitian A., Tambourin P. Spi-1 is a putative oncogene in virally induced murine erythroleukaemias. Nature. 1988 Jan 21;331(6153):277–280. doi: 10.1038/331277a0. [DOI] [PubMed] [Google Scholar]
  39. Moscovici C., Samarut J., Gazzolo L., Moscovici M. G. Myeloid and erythroid neoplastic responses to avian defective leukemia viruses in chickens and in quail. Virology. 1981 Sep;113(2):765–768. doi: 10.1016/0042-6822(81)90205-1. [DOI] [PubMed] [Google Scholar]
  40. Mowat M., Cheng A., Kimura N., Bernstein A., Benchimol S. Rearrangements of the cellular p53 gene in erythroleukaemic cells transformed by Friend virus. Nature. 1985 Apr 18;314(6012):633–636. doi: 10.1038/314633a0. [DOI] [PubMed] [Google Scholar]
  41. Murata M., Eto Y., Shibai H., Sakai M., Muramatsu M. Erythroid differentiation factor is encoded by the same mRNA as that of the inhibin beta A chain. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2434–2438. doi: 10.1073/pnas.85.8.2434. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Nunn M. F., Hunter T. The ets sequence is required for induction of erythroblastosis in chickens by avian retrovirus E26. J Virol. 1989 Jan;63(1):398–402. doi: 10.1128/jvi.63.1.398-402.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Oren M., Levine A. J. Molecular cloning of a cDNA specific for the murine p53 cellular tumor antigen. Proc Natl Acad Sci U S A. 1983 Jan;80(1):56–59. doi: 10.1073/pnas.80.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Paul R., Schuetze S., Kozak S. L., Kabat D. A common site for immortalizing proviral integrations in Friend erythroleukemia: molecular cloning and characterization. J Virol. 1989 Nov;63(11):4958–4961. doi: 10.1128/jvi.63.11.4958-4961.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Paul R., Schuetze S., Kozak S. L., Kozak C. A., Kabat D. The Sfpi-1 proviral integration site of Friend erythroleukemia encodes the ets-related transcription factor Pu.1. J Virol. 1991 Jan;65(1):464–467. doi: 10.1128/jvi.65.1.464-467.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Prochownik E. V., Kukowska J. Deregulated expression of c-myc by murine erythroleukaemia cells prevents differentiation. 1986 Aug 28-Sep 3Nature. 322(6082):848–850. doi: 10.1038/322848a0. [DOI] [PubMed] [Google Scholar]
  47. Prochownik E. V., Kukowska J., Rodgers C. c-myc antisense transcripts accelerate differentiation and inhibit G1 progression in murine erythroleukemia cells. Mol Cell Biol. 1988 Sep;8(9):3683–3695. doi: 10.1128/mcb.8.9.3683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Rabbitts P. H., Forster A., Stinson M. A., Rabbitts T. H. Truncation of exon 1 from the c-myc gene results in prolonged c-myc mRNa stability. EMBO J. 1985 Dec 30;4(13B):3727–3733. doi: 10.1002/j.1460-2075.1985.tb04141.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Radke K., Beug H., Kornfeld S., Graf T. Transformation of both erythroid and myeloid cells by E26, an avian leukemia virus that contains the myb gene. Cell. 1982 Dec;31(3 Pt 2):643–653. doi: 10.1016/0092-8674(82)90320-8. [DOI] [PubMed] [Google Scholar]
  50. Ramsay R. G., Ikeda K., Rifkind R. A., Marks P. A. Changes in gene expression associated with induced differentiation of erythroleukemia: protooncogenes, globin genes, and cell division. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6849–6853. doi: 10.1073/pnas.83.18.6849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Reuben R. C., Wife R. L., Breslow R., Rifkind R. A., Marks P. A. A new group of potent inducers of differentiation in murine erythroleukemia cells. Proc Natl Acad Sci U S A. 1976 Mar;73(3):862–866. doi: 10.1073/pnas.73.3.862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Robert-Lézénès J., Meneceur P., Ray D., Moreau-Gachelin F. Protooncogene expression in normal, preleukemic, and leukemic murine erythroid cells and its relationship to differentiation and proliferation. Cancer Res. 1988 Jul 15;48(14):3972–3976. [PubMed] [Google Scholar]
  53. Rogers S., Wells R., Rechsteiner M. Amino acid sequences common to rapidly degraded proteins: the PEST hypothesis. Science. 1986 Oct 17;234(4774):364–368. doi: 10.1126/science.2876518. [DOI] [PubMed] [Google Scholar]
  54. Ruta M., Clarke S., Boswell B., Kabat D. Heterogeneous metabolism and subcellular localization of a potentially leukemogenic membrane glycoprotein encoded by Friend erythroleukemia virus. Isolation of viral and cellular processing mutants. J Biol Chem. 1982 Jan 10;257(1):126–134. [PubMed] [Google Scholar]
  55. Ruta M., Kabat D. Plasma membrane glycoproteins encoded by cloned Rauscher and Friend spleen focus-forming viruses. J Virol. 1980 Sep;35(3):844–853. doi: 10.1128/jvi.35.3.844-853.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Sariban E., Luebbers R., Kufe D. Transcriptional and posttranscriptional control of c-fos gene expression in human monocytes. Mol Cell Biol. 1988 Jan;8(1):340–346. doi: 10.1128/mcb.8.1.340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Shen-Ong G. L., Keath E. J., Piccoli S. P., Cole M. D. Novel myc oncogene RNA from abortive immunoglobulin-gene recombination in mouse plasmacytomas. Cell. 1982 Dec;31(2 Pt 1):443–452. doi: 10.1016/0092-8674(82)90137-4. [DOI] [PubMed] [Google Scholar]
  58. Shen D. W., Real F. X., DeLeo A. B., Old L. J., Marks P. A., Rifkind R. A. Protein p53 and inducer-mediated erythroleukemia cell commitment to terminal cell division. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5919–5922. doi: 10.1073/pnas.80.19.5919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Sherton C. C., Kabat D. Changes in RNA and protein metabolism preceding onset of hemoglobin synthesis in cultured Friend leukemia cells. Dev Biol. 1976 Jan;48(1):118–131. doi: 10.1016/0012-1606(76)90051-8. [DOI] [PubMed] [Google Scholar]
  60. Shyu A. B., Belasco J. G., Greenberg M. E. Two distinct destabilizing elements in the c-fos message trigger deadenylation as a first step in rapid mRNA decay. Genes Dev. 1991 Feb;5(2):221–231. doi: 10.1101/gad.5.2.221. [DOI] [PubMed] [Google Scholar]
  61. Sobell H. M. Actinomycin and DNA transcription. Proc Natl Acad Sci U S A. 1985 Aug;82(16):5328–5331. doi: 10.1073/pnas.82.16.5328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Spiro C., Gliniak B. C., Kabat D. Splenic accumulation of interleukin-3-dependent hematopoietic cells in Friend erythroleukemia. J Virol. 1989 Oct;63(10):4434–4437. doi: 10.1128/jvi.63.10.4434-4437.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Spiro C., Gliniak B., Kabat D. A tagged helper-free Friend virus causes clonal erythroblast immortality by specific proviral integration in the cellular genome. J Virol. 1988 Nov;62(11):4129–4135. doi: 10.1128/jvi.62.11.4129-4135.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. 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]
  65. Tokunaga K., Taniguchi H., Yoda K., Shimizu M., Sakiyama S. Nucleotide sequence of a full-length cDNA for mouse cytoskeletal beta-actin mRNA. Nucleic Acids Res. 1986 Mar 25;14(6):2829–2829. doi: 10.1093/nar/14.6.2829. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Weber B. L., Westin E. H., Clarke M. F. Differentiation of mouse erythroleukemia cells enhanced by alternatively spliced c-myb mRNA. Science. 1990 Sep 14;249(4974):1291–1293. doi: 10.1126/science.2205003. [DOI] [PubMed] [Google Scholar]
  67. Wendling F., Moreau-Gachelin F., Tambourin P. Emergence of tumorigenic cells during the course of Friend virus leukemias. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3614–3618. doi: 10.1073/pnas.78.6.3614. [DOI] [PMC free article] [PubMed] [Google Scholar]