Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Oct;80(19):5919–5922. doi: 10.1073/pnas.80.19.5919

Protein p53 and inducer-mediated erythroleukemia cell commitment to terminal cell division.

D W Shen, F X Real, A B DeLeo, L J Old, P A Marks, R A Rifkind
PMCID: PMC390188  PMID: 6351070

Abstract

Inducer-mediated murine erythroleukemia cell (MELC) differentiation provides a model for examining factors determining terminal cell differentiation. The nuclear protein, p53, has been implicated as a potential determinant of cell cycle progression and cell differentiation. In this study p53 content and synthesis, during inducer-mediated MELC differentiation, has been examined with monoclonal antibodies to p53. A decrease in p53 synthesis and content was demonstrated during induced differentiation. As determined by cell cycle fractionation, the decrease in p53 is manifest at all stages of the cell cycle. Hemin, which induces globin mRNA accumulation but not terminal cell division, fails to decrease p53 content. A MELC variant resistant to inducer-mediated commitment to terminal cell division also fails to decrease p53 levels in response to inducers. These experiments suggest that p53 is implicated in MELC cell proliferation and that an induced decrease in p53 may be responsible for G1 phase prolongation and terminal G1 arrest.

Full text

PDF
5919

Images in this article

5920Image
on p.5920

Selected References

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

  1. Chandrasekaran K., Mora P. T., Nagarajan L., Anderson W. B. The amount of a specific cellular protein (p53) is a correlate of differentiation in embryonal carcinoma cells. J Cell Physiol. 1982 Oct;113(1):134–140. doi: 10.1002/jcp.1041130122. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. DeLeo A. B., Jay G., Appella E., Dubois G. C., Law L. W., Old L. J. Detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse. Proc Natl Acad Sci U S A. 1979 May;76(5):2420–2424. doi: 10.1073/pnas.76.5.2420. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Deitch A. D., Law H., deVere White R. A stable propidium iodide staining procedure for flow cytometry. J Histochem Cytochem. 1982 Sep;30(9):967–972. doi: 10.1177/30.9.6182188. [DOI] [PubMed] [Google Scholar]
  5. Dippold W. G., Jay G., DeLeo A. B., Khoury G., Old L. J. p53 transformation-related protein: detection by monoclonal antibody in mouse and human cells. Proc Natl Acad Sci U S A. 1981 Mar;78(3):1695–1699. doi: 10.1073/pnas.78.3.1695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fibach E., Reuben R. C., Rifkind R. A., Marks P. A. Effect of hexamethylene bisacetamide on the commitment to differentiation of murine erythroleukemia cells. Cancer Res. 1977 Feb;37(2):440–444. [PubMed] [Google Scholar]
  7. Gambari R., Marks P. A., Rifkind R. A. Murine erythroleukemia cell differentiation: relationship of globin gene expression and of prolongation of G1 to inducer effects during G1/early S. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4511–4515. doi: 10.1073/pnas.76.9.4511. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gambari R., Terada M., Bank A., Rifkind R. A., Marks P. A. Synthesis of globin mRNA in relation to the cell cycle during induced murine erythroleukemia differentiation. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3801–3804. doi: 10.1073/pnas.75.8.3801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Jay G., Shiu R. P., Jay F. T., Levine A. S., Pastan I. Identification of a transformation-specific protein induced by a Rous sarcoma virus. Cell. 1978 Mar;13(3):527–534. doi: 10.1016/0092-8674(78)90326-4. [DOI] [PubMed] [Google Scholar]
  11. Lane D. P., Crawford L. V. T antigen is bound to a host protein in SV40-transformed cells. Nature. 1979 Mar 15;278(5701):261–263. doi: 10.1038/278261a0. [DOI] [PubMed] [Google Scholar]
  12. Linzer D. I., Levine A. J. Characterization of a 54K dalton cellular SV40 tumor antigen present in SV40-transformed cells and uninfected embryonal carcinoma cells. Cell. 1979 May;17(1):43–52. doi: 10.1016/0092-8674(79)90293-9. [DOI] [PubMed] [Google Scholar]
  13. Marks P. A., Chen Z., Banks J., Rifkind R. A. Erythroleukemia cells: variants inducible for hemoglobin synthesis without commitment to terminal cell division. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2281–2284. doi: 10.1073/pnas.80.8.2281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Mercer W. E., Nelson D., DeLeo A. B., Old L. J., Baserga R. Microinjection of monoclonal antibody to protein p53 inhibits serum-induced DNA synthesis in 3T3 cells. Proc Natl Acad Sci U S A. 1982 Oct;79(20):6309–6312. doi: 10.1073/pnas.79.20.6309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Milner J., Milner S. SV40-53K antigen: a possible role for 53K in normal cells. Virology. 1981 Jul 30;112(2):785–788. doi: 10.1016/0042-6822(81)90327-5. [DOI] [PubMed] [Google Scholar]
  17. Mora P. T., Chandrasekaran K., Hoffman J. C., McFarland V. W. Quantitation of a 55K cellular protein: similar amount and instability in normal and malignant mouse cells. Mol Cell Biol. 1982 Jul;2(7):763–771. doi: 10.1128/mcb.2.7.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Novi A. M., Baserga R. Correlation between synthesis of ribosomal RNA and stimulation of DNA synthesis in mouse salivary glands. Lab Invest. 1972 May;26(5):540–547. [PubMed] [Google Scholar]
  19. Nudel U., Salmon J. E., Terada M., Bank A., Rifkind R. A., Marks P. A. Differential effects of chemical inducers on expression of beta globin genes in murine erythroleukemia cells. Proc Natl Acad Sci U S A. 1977 Mar;74(3):1100–1104. doi: 10.1073/pnas.74.3.1100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Oren M., Maltzman W., Levine A. J. Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells. Mol Cell Biol. 1981 Feb;1(2):101–110. doi: 10.1128/mcb.1.2.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Oren M., Reich N. C., Levine A. J. Regulation of the cellular p53 tumor antigen in teratocarcinoma cells and their differentiated progeny. Mol Cell Biol. 1982 Apr;2(4):443–449. doi: 10.1128/mcb.2.4.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Profous-Juchelka H. R., Reuben R. C., Marks P. A., Rifkind R. A. Transcriptional and post-transcriptional regulation of globin gene accumulation in murine erythroleukemia cells. Mol Cell Biol. 1983 Feb;3(2):229–232. doi: 10.1128/mcb.3.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Reuben R. C., Rifkind R. A., Marks P. A. Chemically induced murine erythroleukemic differentiation. Biochim Biophys Acta. 1980 Sep 22;605(3):325–346. doi: 10.1016/0304-419x(80)90015-3. [DOI] [PubMed] [Google Scholar]
  24. Ross J., Sautner D. Induction of globin mRNA accumulation by hemin in cultured erythroleukemic cells. Cell. 1976 Aug;8(4):513–520. doi: 10.1016/0092-8674(76)90219-1. [DOI] [PubMed] [Google Scholar]
  25. Rossow P. W., Riddle V. G., Pardee A. B. Synthesis of labile, serum-dependent protein in early G1 controls animal cell growth. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4446–4450. doi: 10.1073/pnas.76.9.4446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ruscetti S. K., Scolnick E. M. Expression of a transformation-related protein (p53) in the malignant stage of Friend virus-induced diseases. J Virol. 1983 Jun;46(3):1022–1026. doi: 10.1128/jvi.46.3.1022-1026.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sheffery M., Rifkind R. A., Marks P. A. Hexamethylenebisacetamide-resistant murine erythroleukemia cells have altered patterns of inducer-mediated chromatin changes. Proc Natl Acad Sci U S A. 1983 Jun;80(11):3349–3353. doi: 10.1073/pnas.80.11.3349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Singer D., Cooper M., Maniatis G. M., Marks P. A., Rifkind R. A. Erythropoietic differentiation in colonies of cells transformed by Friend virus. Proc Natl Acad Sci U S A. 1974 Jul;71(7):2668–2670. doi: 10.1073/pnas.71.7.2668. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES