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. 1982 Apr;2(4):443–449. doi: 10.1128/mcb.2.4.443

Regulation of the cellular p53 tumor antigen in teratocarcinoma cells and their differentiated progeny.

M Oren, N C Reich, A J Levine
PMCID: PMC369808  PMID: 6287239

Abstract

F9 embryonal carcinoma cells express high levels of a 53,000-molecular-weight cellular tumor antigen called p53. When F9 cell cultures are treated with retinoic acid and dibutyryl adenosine 3',5'-phosphate, they differentiate, predominantly into endoderm-like cells. This differentiation is accompanied by a marked decrease in the levels of p53. The mechanism(s) responsible for this decline in the level of p53 in differentiated cells was investigated. The results demonstrate that the high levels of p53 in F9 cells relative to their differentiated progeny were not due to alterations in the stability or turnover of this protein. Rather, the regulation during differentiation involved a marked decrease in the amount of in vitro translatable p53 mRNA detected in the differentiated cell cultures. This mechanism is unlike the one operating during the simian virus 40 infection or transformation, where the increased levels of p53 are largely due to the increased stability of the p53 protein.

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Selected References

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

  1. Berstine E. G., Hooper M. L., Grandchamp S., Ephrussi B. Alkaline phosphatase activity in mouse teratoma. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3899–3903. doi: 10.1073/pnas.70.12.3899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Crawford L. V., Pim D. C., Gurney E. G., Goodfellow P., Taylor-Papadimitriou J. Detection of a common feature in several human tumor cell lines--a 53,000-dalton protein. Proc Natl Acad Sci U S A. 1981 Jan;78(1):41–45. doi: 10.1073/pnas.78.1.41. [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. 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]
  5. Fanning E., Nowak B., Burger C. Detection and characterization of multiple forms of simian virus 40 large T antigen. J Virol. 1981 Jan;37(1):92–102. doi: 10.1128/jvi.37.1.92-102.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Linzer D. I., Maltzman W., Levine A. J. The SV40 A gene product is required for the production of a 54,000 MW cellular tumor antigen. Virology. 1979 Oct 30;98(2):308–318. doi: 10.1016/0042-6822(79)90554-3. [DOI] [PubMed] [Google Scholar]
  9. Luka J., Jörnvall H., Klein G. Purification and biochemical characterization of the Epstein-Barr virus-determined nuclear antigen and an associated protein with a 53,000-dalton subunit. J Virol. 1980 Sep;35(3):592–602. doi: 10.1128/jvi.35.3.592-602.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Maltzman W., Oren M., Levine A. J. The structural relationships between 54,000-molecular-weight cellular tumor antigens detected in viral- and nonviral-transformed cells. Virology. 1981 Jul 15;112(1):145–156. doi: 10.1016/0042-6822(81)90620-6. [DOI] [PubMed] [Google Scholar]
  11. McCormick F., Clark R., Harlow E., Tjian R. SV40 T antigen binds specifically to a cellular 53 K protein in vitro. Nature. 1981 Jul 2;292(5818):63–65. doi: 10.1038/292063a0. [DOI] [PubMed] [Google Scholar]
  12. McCormick F., Harlow E. Association of a murine 53,000-dalton phosphoprotein with simian virus 40 large-T antigen in transformed cells. J Virol. 1980 Apr;34(1):213–224. doi: 10.1128/jvi.34.1.213-224.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mora P. T., Chandrasekaran K., McFarland V. W. An embryo protein induced by SV40 virus transformation of mouse cells. Nature. 1980 Dec 25;288(5792):722–724. doi: 10.1038/288722a0. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Pelham H. R., Jackson R. J. An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem. 1976 Aug 1;67(1):247–256. doi: 10.1111/j.1432-1033.1976.tb10656.x. [DOI] [PubMed] [Google Scholar]
  16. Rotter V., Boss M. A., Baltimore D. Increased concentration of an apparently identical cellular protein in cells transformed by either Abelson murine leukemia virus or other transforming agents. J Virol. 1981 Apr;38(1):336–346. doi: 10.1128/jvi.38.1.336-346.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Segal S., Khoury G. Differentiation as a requirement for simian virus 40 gene expression in F-9 embryonal carcinoma cells. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5611–5615. doi: 10.1073/pnas.76.11.5611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Segal S., Levine A. J., Khoury G. Evidence for non-spliced SV40 RNA in undifferentiated murine teratocarcinoma stem cells. Nature. 1979 Jul 26;280(5720):335–338. doi: 10.1038/280335a0. [DOI] [PubMed] [Google Scholar]
  19. Smith A. E., Smith R., Paucha E. Characterization of different tumor antigens present in cells transformed by simian virus 40. Cell. 1979 Oct;18(2):335–346. doi: 10.1016/0092-8674(79)90053-9. [DOI] [PubMed] [Google Scholar]
  20. Strickland S., Mahdavi V. The induction of differentiation in teratocarcinoma stem cells by retinoic acid. Cell. 1978 Oct;15(2):393–403. doi: 10.1016/0092-8674(78)90008-9. [DOI] [PubMed] [Google Scholar]
  21. Strickland S., Sawey M. J. Studies on the effect of retinoids on the differentiation of teratocarcinoma stem cells in vitro and in vivo. Dev Biol. 1980 Jul;78(1):76–85. doi: 10.1016/0012-1606(80)90319-x. [DOI] [PubMed] [Google Scholar]
  22. Strickland S., Smith K. K., Marotti K. R. Hormonal induction of differentiation in teratocarcinoma stem cells: generation of parietal endoderm by retinoic acid and dibutyryl cAMP. Cell. 1980 Sep;21(2):347–355. doi: 10.1016/0092-8674(80)90471-7. [DOI] [PubMed] [Google Scholar]

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