Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1993 Mar;13(3):1456–1463. doi: 10.1128/mcb.13.3.1456

Growth suppression of Friend virus-transformed erythroleukemia cells by p53 protein is accompanied by hemoglobin production and is sensitive to erythropoietin.

P Johnson 1, S Chung 1, S Benchimol 1
PMCID: PMC359456  PMID: 8441390

Abstract

The murine allele temperature-sensitive (ts) p53Val-135 encodes a ts p53 protein that behaves as a mutant polypeptide at 37 degrees C and as a wild-type polypeptide at 32 degrees C. This ts allele was introduced into the p53 nonproducer Friend erythroleukemia cell line DP16-1. The DP16-1 cell line was derived from the spleen cells of a mouse infected with the polycythemia strain of Friend virus, and like other erythroleukemia cell lines transformed by this virus, it grows independently of erythropoietin, likely because of expression of the viral gp55 protein which binds to and activates the erythropoietin receptor. When incubated at 32 degrees C, DP16-1 cells expressing ts p53Val-135 protein, arrested in the G0/G1 phase of the cell cycle, rapidly lost viability and expressed hemoglobin, a marker of erythroid differentiation. Erythropoietin had a striking effect on p53Val-135-expressing cells at 32 degrees C by prolonging their survival and diminishing the extent of hemoglobin production. This response to erythropoietin was not accompanied by down-regulation of viral gp55 protein.

Full text

PDF
1456

Images in this article

1458Image
on p.1458
1460Image
on p.1460
1461Image
on p.1461

Selected References

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

  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., Bernstein A. Identification and mapping of a common proviral integration site Fli-1 in erythroleukemia cells induced by Friend murine leukemia virus. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1332–1336. doi: 10.1073/pnas.87.4.1332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Caron de Fromentel C., Soussi T. TP53 tumor suppressor gene: a model for investigating human mutagenesis. Genes Chromosomes Cancer. 1992 Jan;4(1):1–15. doi: 10.1002/gcc.2870040102. [DOI] [PubMed] [Google Scholar]
  4. Chen P. L., Chen Y. M., Bookstein R., Lee W. H. Genetic mechanisms of tumor suppression by the human p53 gene. Science. 1990 Dec 14;250(4987):1576–1580. doi: 10.1126/science.2274789. [DOI] [PubMed] [Google Scholar]
  5. D'Andrea A. D., Zon L. I. Erythropoietin receptor. Subunit structure and activation. J Clin Invest. 1990 Sep;86(3):681–687. doi: 10.1172/JCI114763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Diller L., Kassel J., Nelson C. E., Gryka M. A., Litwak G., Gebhardt M., Bressac B., Ozturk M., Baker S. J., Vogelstein B. p53 functions as a cell cycle control protein in osteosarcomas. Mol Cell Biol. 1990 Nov;10(11):5772–5781. doi: 10.1128/mcb.10.11.5772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Donehower L. A., Harvey M., Slagle B. L., McArthur M. J., Montgomery C. A., Jr, Butel J. S., Bradley A. Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature. 1992 Mar 19;356(6366):215–221. doi: 10.1038/356215a0. [DOI] [PubMed] [Google Scholar]
  8. Eliyahu D., Goldfinger N., Pinhasi-Kimhi O., Shaulsky G., Skurnik Y., Arai N., Rotter V., Oren M. Meth A fibrosarcoma cells express two transforming mutant p53 species. Oncogene. 1988 Sep;3(3):313–321. [PubMed] [Google Scholar]
  9. Finlay C. A., Hinds P. W., Tan T. H., Eliyahu D., Oren M., Levine A. J. Activating mutations for transformation by p53 produce a gene product that forms an hsc70-p53 complex with an altered half-life. Mol Cell Biol. 1988 Feb;8(2):531–539. doi: 10.1128/mcb.8.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Friedman E. A., Schildkraut C. L. Lengthening of the G1 phase is not strictly correlated with differentiation in Friend erythroleukemia cells. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3813–3817. doi: 10.1073/pnas.75.8.3813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gannon J. V., Greaves R., Iggo R., Lane D. P. Activating mutations in p53 produce a common conformational effect. A monoclonal antibody specific for the mutant form. EMBO J. 1990 May;9(5):1595–1602. doi: 10.1002/j.1460-2075.1990.tb08279.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Ginsberg D., Michael-Michalovitz D., Ginsberg D., Oren M. Induction of growth arrest by a temperature-sensitive p53 mutant is correlated with increased nuclear localization and decreased stability of the protein. Mol Cell Biol. 1991 Jan;11(1):582–585. doi: 10.1128/mcb.11.1.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Harlow E., Crawford L. V., Pim D. C., Williamson N. M. Monoclonal antibodies specific for simian virus 40 tumor antigens. J Virol. 1981 Sep;39(3):861–869. doi: 10.1128/jvi.39.3.861-869.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hicks G. G., Mowat M. Integration of Friend murine leukemia virus into both alleles of the p53 oncogene in an erythroleukemic cell line. J Virol. 1988 Dec;62(12):4752–4755. doi: 10.1128/jvi.62.12.4752-4755.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  19. Johnson P., Benchimol S. Friend virus induced murine erythroleukaemia: the p53 locus. Cancer Surv. 1992;12:137–151. [PubMed] [Google Scholar]
  20. Johnson P., Gray D., Mowat M., Benchimol S. Expression of wild-type p53 is not compatible with continued growth of p53-negative tumor cells. Mol Cell Biol. 1991 Jan;11(1):1–11. doi: 10.1128/mcb.11.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kaiho S., Mizuno K. Sensitive assay systems for detection of hemoglobin with 2,7-diaminofluorene: histochemistry and colorimetry for erythrodifferentiation. Anal Biochem. 1985 Aug 15;149(1):117–120. doi: 10.1016/0003-2697(85)90483-x. [DOI] [PubMed] [Google Scholar]
  22. Kastan M. B., Onyekwere O., Sidransky D., Vogelstein B., Craig R. W. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 1991 Dec 1;51(23 Pt 1):6304–6311. [PubMed] [Google Scholar]
  23. 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]
  24. Koury M. J., Bondurant M. C. Erythropoietin retards DNA breakdown and prevents programmed death in erythroid progenitor cells. Science. 1990 Apr 20;248(4953):378–381. doi: 10.1126/science.2326648. [DOI] [PubMed] [Google Scholar]
  25. Koury M. J., Bondurant M. C. Maintenance by erythropoietin of viability and maturation of murine erythroid precursor cells. J Cell Physiol. 1988 Oct;137(1):65–74. doi: 10.1002/jcp.1041370108. [DOI] [PubMed] [Google Scholar]
  26. Krantz S. B. Erythropoietin. Blood. 1991 Feb 1;77(3):419–434. [PubMed] [Google Scholar]
  27. Kuerbitz S. J., Plunkett B. S., Walsh W. V., Kastan M. B. Wild-type p53 is a cell cycle checkpoint determinant following irradiation. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7491–7495. doi: 10.1073/pnas.89.16.7491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Lane D. P. Cancer. p53, guardian of the genome. Nature. 1992 Jul 2;358(6381):15–16. doi: 10.1038/358015a0. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Linnekin D., Evans G. A., D'Andrea A., Farrar W. L. Association of the erythropoietin receptor with protein tyrosine kinase activity. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6237–6241. doi: 10.1073/pnas.89.14.6237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Longmore G. D., Lodish H. F. An activating mutation in the murine erythropoietin receptor induces erythroleukemia in mice: a cytokine receptor superfamily oncogene. Cell. 1991 Dec 20;67(6):1089–1102. doi: 10.1016/0092-8674(91)90286-8. [DOI] [PubMed] [Google Scholar]
  32. Mager D. L., Mak T. W., Bernstein A. Quantitative colony method for tumorigenic cells transformed by two distinct strains of Friend leukemia virus. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1703–1707. doi: 10.1073/pnas.78.3.1703. [DOI] [PMC free article] [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. Martinez J., Georgoff I., Martinez J., Levine A. J. Cellular localization and cell cycle regulation by a temperature-sensitive p53 protein. Genes Dev. 1991 Feb;5(2):151–159. doi: 10.1101/gad.5.2.151. [DOI] [PubMed] [Google Scholar]
  35. Mercer W. E., Amin M., Sauve G. J., Appella E., Ullrich S. J., Romano J. W. Wild type human p53 is antiproliferative in SV40-transformed hamster cells. Oncogene. 1990 Jul;5(7):973–980. [PubMed] [Google Scholar]
  36. Mercer W. E., Shields M. T., Amin M., Sauve G. J., Appella E., Romano J. W., Ullrich S. J. Negative growth regulation in a glioblastoma tumor cell line that conditionally expresses human wild-type p53. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6166–6170. doi: 10.1073/pnas.87.16.6166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Michalovitz D., Halevy O., Oren M. Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53. Cell. 1990 Aug 24;62(4):671–680. doi: 10.1016/0092-8674(90)90113-s. [DOI] [PubMed] [Google Scholar]
  38. Migliaccio A. R., Migliaccio G., D'Andrea A., Baiocchi M., Crotta S., Nicolis S., Ottolenghi S., Adamson J. W. Response to erythropoietin in erythroid subclones of the factor-dependent cell line 32D is determined by translocation of the erythropoietin receptor to the cell surface. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11086–11090. doi: 10.1073/pnas.88.24.11086. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  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. Munroe D. G., Peacock J. W., Benchimol S. Inactivation of the cellular p53 gene is a common feature of Friend virus-induced erythroleukemia: relationship of inactivation to dominant transforming alleles. Mol Cell Biol. 1990 Jul;10(7):3307–3313. doi: 10.1128/mcb.10.7.3307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Ruscetti S. K., Janesch N. J., Chakraborti A., Sawyer S. T., Hankins W. D. Friend spleen focus-forming virus induces factor independence in an erythropoietin-dependent erythroleukemia cell line. J Virol. 1990 Mar;64(3):1057–1062. doi: 10.1128/jvi.64.3.1057-1062.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Ruscetti S., Wolff L. Spleen focus-forming virus: relationship of an altered envelope gene to the development of a rapid erythroleukemia. Curr Top Microbiol Immunol. 1984;112:21–44. doi: 10.1007/978-3-642-69677-0_2. [DOI] [PubMed] [Google Scholar]
  44. 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]
  45. Shaulsky G., Goldfinger N., Peled A., Rotter V. Involvement of wild-type p53 in pre-B-cell differentiation in vitro. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8982–8986. doi: 10.1073/pnas.88.20.8982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tambourin P. E., Wendling F., Jasmin C., Smadja-Joffe F. The physiopathology of Friend leukemia. Leuk Res. 1979;3(3):117–129. doi: 10.1016/0145-2126(79)90009-2. [DOI] [PubMed] [Google Scholar]
  47. Terada M., Fried J., Nudel U., Rifkind R. A., Marks P. A. Transient inhibition of initiation of S-phase associated with dimethyl sulfoxide induction of murine erythroleukemia cells to erythroid differentiation. Proc Natl Acad Sci U S A. 1977 Jan;74(1):248–252. doi: 10.1073/pnas.74.1.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Yewdell J. W., Gannon J. V., Lane D. P. Monoclonal antibody analysis of p53 expression in normal and transformed cells. J Virol. 1986 Aug;59(2):444–452. doi: 10.1128/jvi.59.2.444-452.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Yonish-Rouach E., Resnitzky D., Lotem J., Sachs L., Kimchi A., Oren M. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature. 1991 Jul 25;352(6333):345–347. doi: 10.1038/352345a0. [DOI] [PubMed] [Google Scholar]
  50. Yoshimura A., D'Andrea A. D., Lodish H. F. Friend spleen focus-forming virus glycoprotein gp55 interacts with the erythropoietin receptor in the endoplasmic reticulum and affects receptor metabolism. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4139–4143. doi: 10.1073/pnas.87.11.4139. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES