Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1995 Jun;15(6):3032–3040. doi: 10.1128/mcb.15.6.3032

Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression.

L B Owen-Schaub 1, W Zhang 1, J C Cusack 1, L S Angelo 1, S M Santee 1, T Fujiwara 1, J A Roth 1, A B Deisseroth 1, W W Zhang 1, E Kruzel 1, et al.
PMCID: PMC230534  PMID: 7539102

Abstract

Fas/APO-1 is a cell surface protein known to trigger apoptosis upon specific antibody engagement. Because wild-type p53 can activate transcription as well as induce apoptosis, we queried whether p53 might upregulate Fas/APO-1. To explore this possibility, we examined human p53-null (H358 non-small-cell lung adenocarcinoma and K562 erythroleukemia) and wild-type p53-containing (H460 non-small-cell lung adenocarcinoma) cell lines. When H358 or H460 cells were transduced with a replication-deficient adenovirus expression construct containing the human wild-type p53 gene but not with vector alone, a marked upregulation (approximately a three-to fourfold increase) of cell surface Fas/APO-1 was observed by flow cytometry. Similarly, K562, cells stably transfected with a plasmid vector containing the temperature-sensitive human p53 mutant Ala-143 demonstrated a four- to sixfold upregulation of Fas/APO-1 by flow-cytometric analysis at the permissive temperature of 32.5 degrees C. Temperature-sensitive upregulation of Fas/APO-1 in K562 Ala-143 cells was verified by immunoprecipitation and demonstrated to result from enhanced mRNA production by nuclear run-on and Northern (RNA) analyses. Stably transfected K562 cells expressing temperature-insensitive, transcriptionally inactive p53 mutants (His-175, Trp-248, His-273, or Gly-281) failed to upregulate Fas/APO-1 at either 32.5 degrees or 37.5 degrees C. The temperature-sensitive transcription of Fas/APO-1 occurred in the presence of cycloheximide, indicating that de novo protein synthesis was not required and suggested a direct involvement of p53. Collectively, these observations argue that Fas/APO-1 is a target gene for transcriptional activation by p53.

Full Text

The Full Text of this article is available as a PDF (438.5 KB).

Selected References

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

  1. Adachi M., Watanabe-Fukunaga R., Nagata S. Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1756–1760. doi: 10.1073/pnas.90.5.1756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Agoff S. N., Hou J., Linzer D. I., Wu B. Regulation of the human hsp70 promoter by p53. Science. 1993 Jan 1;259(5091):84–87. doi: 10.1126/science.8418500. [DOI] [PubMed] [Google Scholar]
  3. Alderson M. R., Tough T. W., Davis-Smith T., Braddy S., Falk B., Schooley K. A., Goodwin R. G., Smith C. A., Ramsdell F., Lynch D. H. Fas ligand mediates activation-induced cell death in human T lymphocytes. J Exp Med. 1995 Jan 1;181(1):71–77. doi: 10.1084/jem.181.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baker S. J., Markowitz S., Fearon E. R., Willson J. K., Vogelstein B. Suppression of human colorectal carcinoma cell growth by wild-type p53. Science. 1990 Aug 24;249(4971):912–915. doi: 10.1126/science.2144057. [DOI] [PubMed] [Google Scholar]
  5. Barak Y., Juven T., Haffner R., Oren M. mdm2 expression is induced by wild type p53 activity. EMBO J. 1993 Feb;12(2):461–468. doi: 10.1002/j.1460-2075.1993.tb05678.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Behrmann I., Walczak H., Krammer P. H. Structure of the human APO-1 gene. Eur J Immunol. 1994 Dec;24(12):3057–3062. doi: 10.1002/eji.1830241221. [DOI] [PubMed] [Google Scholar]
  7. Borellini F., Glazer R. I. Induction of Sp1-p53 DNA-binding heterocomplexes during granulocyte/macrophage colony-stimulating factor-dependent proliferation in human erythroleukemia cell line TF-1. J Biol Chem. 1993 Apr 15;268(11):7923–7928. [PubMed] [Google Scholar]
  8. Caelles C., Helmberg A., Karin M. p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature. 1994 Jul 21;370(6486):220–223. doi: 10.1038/370220a0. [DOI] [PubMed] [Google Scholar]
  9. Chen J. Y., Funk W. D., Wright W. E., Shay J. W., Minna J. D. Heterogeneity of transcriptional activity of mutant p53 proteins and p53 DNA target sequences. Oncogene. 1993 Aug;8(8):2159–2166. [PubMed] [Google Scholar]
  10. Cheng J., Liu C., Koopman W. J., Mountz J. D. Characterization of human Fas gene. Exon/intron organization and promoter region. J Immunol. 1995 Feb 1;154(3):1239–1245. [PubMed] [Google Scholar]
  11. Chu J. L., Drappa J., Parnassa A., Elkon K. B. The defect in Fas mRNA expression in MRL/lpr mice is associated with insertion of the retrotransposon, ETn. J Exp Med. 1993 Aug 1;178(2):723–730. doi: 10.1084/jem.178.2.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Clarke A. R., Purdie C. A., Harrison D. J., Morris R. G., Bird C. C., Hooper M. L., Wyllie A. H. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature. 1993 Apr 29;362(6423):849–852. doi: 10.1038/362849a0. [DOI] [PubMed] [Google Scholar]
  13. Cohen P. L., Eisenberg R. A. Lpr and gld: single gene models of systemic autoimmunity and lymphoproliferative disease. Annu Rev Immunol. 1991;9:243–269. doi: 10.1146/annurev.iy.09.040191.001331. [DOI] [PubMed] [Google Scholar]
  14. Deb S. P., Muñoz R. M., Brown D. R., Subler M. A., Deb S. Wild-type human p53 activates the human epidermal growth factor receptor promoter. Oncogene. 1994 May;9(5):1341–1349. [PubMed] [Google Scholar]
  15. 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]
  16. Eliyahu D., Michalovitz D., Eliyahu S., Pinhasi-Kimhi O., Oren M. Wild-type p53 can inhibit oncogene-mediated focus formation. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8763–8767. doi: 10.1073/pnas.86.22.8763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Farmer G., Bargonetti J., Zhu H., Friedman P., Prywes R., Prives C. Wild-type p53 activates transcription in vitro. Nature. 1992 Jul 2;358(6381):83–86. doi: 10.1038/358083a0. [DOI] [PubMed] [Google Scholar]
  18. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  19. Fields S., Jang S. K. Presence of a potent transcription activating sequence in the p53 protein. Science. 1990 Aug 31;249(4972):1046–1049. doi: 10.1126/science.2144363. [DOI] [PubMed] [Google Scholar]
  20. Finlay C. A., Hinds P. W., Levine A. J. The p53 proto-oncogene can act as a suppressor of transformation. Cell. 1989 Jun 30;57(7):1083–1093. doi: 10.1016/0092-8674(89)90045-7. [DOI] [PubMed] [Google Scholar]
  21. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Fujiwara T., Grimm E. A., Mukhopadhyay T., Zhang W. W., Owen-Schaub L. B., Roth J. A. Induction of chemosensitivity in human lung cancer cells in vivo by adenovirus-mediated transfer of the wild-type p53 gene. Cancer Res. 1994 May 1;54(9):2287–2291. [PubMed] [Google Scholar]
  23. Funk W. D., Pak D. T., Karas R. H., Wright W. E., Shay J. W. A transcriptionally active DNA-binding site for human p53 protein complexes. Mol Cell Biol. 1992 Jun;12(6):2866–2871. doi: 10.1128/mcb.12.6.2866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hanabuchi S., Koyanagi M., Kawasaki A., Shinohara N., Matsuzawa A., Nishimura Y., Kobayashi Y., Yonehara S., Yagita H., Okumura K. Fas and its ligand in a general mechanism of T-cell-mediated cytotoxicity. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4930–4934. doi: 10.1073/pnas.91.11.4930. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Harper J. W., Adami G. R., Wei N., Keyomarsi K., Elledge S. J. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 1993 Nov 19;75(4):805–816. doi: 10.1016/0092-8674(93)90499-g. [DOI] [PubMed] [Google Scholar]
  26. Hashimoto S., Ishii A., Yonehara S. The E1b oncogene of adenovirus confers cellular resistance to cytotoxicity of tumor necrosis factor and monoclonal anti-Fas antibody. Int Immunol. 1991 Apr;3(4):343–351. doi: 10.1093/intimm/3.4.343. [DOI] [PubMed] [Google Scholar]
  27. Itoh N., Tsujimoto Y., Nagata S. Effect of bcl-2 on Fas antigen-mediated cell death. J Immunol. 1993 Jul 15;151(2):621–627. [PubMed] [Google Scholar]
  28. Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
  29. Johnson P., Chung S., Benchimol S. Growth suppression of Friend virus-transformed erythroleukemia cells by p53 protein is accompanied by hemoglobin production and is sensitive to erythropoietin. Mol Cell Biol. 1993 Mar;13(3):1456–1463. doi: 10.1128/mcb.13.3.1456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Kastan M. B., Zhan Q., el-Deiry W. S., Carrier F., Jacks T., Walsh W. V., Plunkett B. S., Vogelstein B., Fornace A. J., Jr A mammalian cell cycle checkpoint pathway utilizing p53 and GADD45 is defective in ataxia-telangiectasia. Cell. 1992 Nov 13;71(4):587–597. doi: 10.1016/0092-8674(92)90593-2. [DOI] [PubMed] [Google Scholar]
  32. Kern S. E., Kinzler K. W., Bruskin A., Jarosz D., Friedman P., Prives C., Vogelstein B. Identification of p53 as a sequence-specific DNA-binding protein. Science. 1991 Jun 21;252(5013):1708–1711. doi: 10.1126/science.2047879. [DOI] [PubMed] [Google Scholar]
  33. Kern S. E., Pietenpol J. A., Thiagalingam S., Seymour A., Kinzler K. W., Vogelstein B. Oncogenic forms of p53 inhibit p53-regulated gene expression. Science. 1992 May 8;256(5058):827–830. doi: 10.1126/science.1589764. [DOI] [PubMed] [Google Scholar]
  34. Koeffler H. P., Miller C., Nicolson M. A., Ranyard J., Bosselman R. A. Increased expression of p53 protein in human leukemia cells. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4035–4039. doi: 10.1073/pnas.83.11.4035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. 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]
  36. Leithäuser F., Dhein J., Mechtersheimer G., Koretz K., Brüderlein S., Henne C., Schmidt A., Debatin K. M., Krammer P. H., Möller P. Constitutive and induced expression of APO-1, a new member of the nerve growth factor/tumor necrosis factor receptor superfamily, in normal and neoplastic cells. Lab Invest. 1993 Oct;69(4):415–429. [PubMed] [Google Scholar]
  37. Livingstone L. R., White A., Sprouse J., Livanos E., Jacks T., Tlsty T. D. Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell. 1992 Sep 18;70(6):923–935. doi: 10.1016/0092-8674(92)90243-6. [DOI] [PubMed] [Google Scholar]
  38. Lowe S. W., Schmitt E. M., Smith S. W., Osborne B. A., Jacks T. p53 is required for radiation-induced apoptosis in mouse thymocytes. Nature. 1993 Apr 29;362(6423):847–849. doi: 10.1038/362847a0. [DOI] [PubMed] [Google Scholar]
  39. McGahon A., Bissonnette R., Schmitt M., Cotter K. M., Green D. R., Cotter T. G. BCR-ABL maintains resistance of chronic myelogenous leukemia cells to apoptotic cell death. Blood. 1994 Mar 1;83(5):1179–1187. [PubMed] [Google Scholar]
  40. 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]
  41. 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]
  42. Mitsudomi T., Steinberg S. M., Nau M. M., Carbone D., D'Amico D., Bodner S., Oie H. K., Linnoila R. I., Mulshine J. L., Minna J. D. p53 gene mutations in non-small-cell lung cancer cell lines and their correlation with the presence of ras mutations and clinical features. Oncogene. 1992 Jan;7(1):171–180. [PubMed] [Google Scholar]
  43. Miyashita T., Krajewski S., Krajewska M., Wang H. G., Lin H. K., Liebermann D. A., Hoffman B., Reed J. C. Tumor suppressor p53 is a regulator of bcl-2 and bax gene expression in vitro and in vivo. Oncogene. 1994 Jun;9(6):1799–1805. [PubMed] [Google Scholar]
  44. Morimoto H., Yonehara S., Bonavida B. Overcoming tumor necrosis factor and drug resistance of human tumor cell lines by combination treatment with anti-Fas antibody and drugs or toxins. Cancer Res. 1993 Jun 1;53(11):2591–2596. [PubMed] [Google Scholar]
  45. Mountz J. D., Bluethmann H., Zhou T., Wu J. Defective clonal deletion and anergy induction in TCR transgenic lpr/lpr mice. Semin Immunol. 1994 Feb;6(1):27–37. doi: 10.1006/smim.1994.1005. [DOI] [PubMed] [Google Scholar]
  46. Oehm A., Behrmann I., Falk W., Pawlita M., Maier G., Klas C., Li-Weber M., Richards S., Dhein J., Trauth B. C. Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen. J Biol Chem. 1992 May 25;267(15):10709–10715. [PubMed] [Google Scholar]
  47. Oltvai Z. N., Milliman C. L., Korsmeyer S. J. Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 1993 Aug 27;74(4):609–619. doi: 10.1016/0092-8674(93)90509-o. [DOI] [PubMed] [Google Scholar]
  48. Owen-Schaub L. B., Radinsky R., Kruzel E., Berry K., Yonehara S. Anti-Fas on nonhematopoietic tumors: levels of Fas/APO-1 and bcl-2 are not predictive of biological responsiveness. Cancer Res. 1994 Mar 15;54(6):1580–1586. [PubMed] [Google Scholar]
  49. Owen-Schaub L. B., Yonehara S., Crump W. L., 3rd, Grimm E. A. DNA fragmentation and cell death is selectively triggered in activated human lymphocytes by Fas antigen engagement. Cell Immunol. 1992 Mar;140(1):197–205. doi: 10.1016/0008-8749(92)90187-t. [DOI] [PubMed] [Google Scholar]
  50. Radinsky R., Culp L. A. Clonal dominance of select subsets of viral Kirsten ras(+)-transformed 3T3 cells during tumor progression. Int J Cancer. 1991 Apr 22;48(1):148–159. doi: 10.1002/ijc.2910480126. [DOI] [PubMed] [Google Scholar]
  51. Radinsky R., Fidler I. J., Price J. E., Esumi N., Tsan R., Petty C. M., Bucana C. D., Bar-Eli M. Terminal differentiation and apoptosis in experimental lung metastases of human osteogenic sarcoma cells by wild type p53. Oncogene. 1994 Jul;9(7):1877–1883. [PubMed] [Google Scholar]
  52. Radinsky R., Kraemer P. M., Raines M. A., Kung H. J., Culp L. A. Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5143–5147. doi: 10.1073/pnas.84.15.5143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Ramqvist T., Magnusson K. P., Wang Y., Szekely L., Klein G., Wiman K. G. Wild-type p53 induces apoptosis in a Burkitt lymphoma (BL) line that carries mutant p53. Oncogene. 1993 Jun;8(6):1495–1500. [PubMed] [Google Scholar]
  54. Raycroft L., Wu H. Y., Lozano G. Transcriptional activation by wild-type but not transforming mutants of the p53 anti-oncogene. Science. 1990 Aug 31;249(4972):1049–1051. doi: 10.1126/science.2144364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Rouvier E., Luciani M. F., Golstein P. Fas involvement in Ca(2+)-independent T cell-mediated cytotoxicity. J Exp Med. 1993 Jan 1;177(1):195–200. doi: 10.1084/jem.177.1.195. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Russell J. H., Rush B., Weaver C., Wang R. Mature T cells of autoimmune lpr/lpr mice have a defect in antigen-stimulated suicide. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4409–4413. doi: 10.1073/pnas.90.10.4409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Ryan J. J., Danish R., Gottlieb C. A., Clarke M. F. Cell cycle analysis of p53-induced cell death in murine erythroleukemia cells. Mol Cell Biol. 1993 Jan;13(1):711–719. doi: 10.1128/mcb.13.1.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Schärer E., Iggo R. Mammalian p53 can function as a transcription factor in yeast. Nucleic Acids Res. 1992 Apr 11;20(7):1539–1545. doi: 10.1093/nar/20.7.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Shaw P., Bovey R., Tardy S., Sahli R., Sordat B., Costa J. Induction of apoptosis by wild-type p53 in a human colon tumor-derived cell line. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4495–4499. doi: 10.1073/pnas.89.10.4495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Stalder T., Hahn S., Erb P. Fas antigen is the major target molecule for CD4+ T cell-mediated cytotoxicity. J Immunol. 1994 Feb 1;152(3):1127–1133. [PubMed] [Google Scholar]
  61. Suda T., Takahashi T., Golstein P., Nagata S. Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family. Cell. 1993 Dec 17;75(6):1169–1178. doi: 10.1016/0092-8674(93)90326-l. [DOI] [PubMed] [Google Scholar]
  62. Symonds H., Krall L., Remington L., Saenz-Robles M., Lowe S., Jacks T., Van Dyke T. p53-dependent apoptosis suppresses tumor growth and progression in vivo. Cell. 1994 Aug 26;78(4):703–711. doi: 10.1016/0092-8674(94)90534-7. [DOI] [PubMed] [Google Scholar]
  63. Takahashi T., Nau M. M., Chiba I., Birrer M. J., Rosenberg R. K., Vinocour M., Levitt M., Pass H., Gazdar A. F., Minna J. D. p53: a frequent target for genetic abnormalities in lung cancer. Science. 1989 Oct 27;246(4929):491–494. doi: 10.1126/science.2554494. [DOI] [PubMed] [Google Scholar]
  64. Takahashi T., Tanaka M., Brannan C. I., Jenkins N. A., Copeland N. G., Suda T., Nagata S. Generalized lymphoproliferative disease in mice, caused by a point mutation in the Fas ligand. Cell. 1994 Mar 25;76(6):969–976. doi: 10.1016/0092-8674(94)90375-1. [DOI] [PubMed] [Google Scholar]
  65. Trauth B. C., Klas C., Peters A. M., Matzku S., Möller P., Falk W., Debatin K. M., Krammer P. H. Monoclonal antibody-mediated tumor regression by induction of apoptosis. Science. 1989 Jul 21;245(4915):301–305. doi: 10.1126/science.2787530. [DOI] [PubMed] [Google Scholar]
  66. Vignaux F., Golstein P. Fas-based lymphocyte-mediated cytotoxicity against syngeneic activated lymphocytes: a regulatory pathway? Eur J Immunol. 1994 Apr;24(4):923–927. doi: 10.1002/eji.1830240421. [DOI] [PubMed] [Google Scholar]
  67. Wang Y., Ramqvist T., Szekely L., Axelson H., Klein G., Wiman K. G. Reconstitution of wild-type p53 expression triggers apoptosis in a p53-negative v-myc retrovirus-induced T-cell lymphoma line. Cell Growth Differ. 1993 Jun;4(6):467–473. [PubMed] [Google Scholar]
  68. Watanabe-Fukunaga R., Brannan C. I., Copeland N. G., Jenkins N. A., Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992 Mar 26;356(6367):314–317. doi: 10.1038/356314a0. [DOI] [PubMed] [Google Scholar]
  69. Weintraub H., Hauschka S., Tapscott S. J. The MCK enhancer contains a p53 responsive element. Proc Natl Acad Sci U S A. 1991 Jun 1;88(11):4570–4571. doi: 10.1073/pnas.88.11.4570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Wilkinson M. F., MacLeod C. L. Induction of T-cell receptor-alpha and -beta mRNA in SL12 cells can occur by transcriptional and post-transcriptional mechanisms. EMBO J. 1988 Jan;7(1):101–109. doi: 10.1002/j.1460-2075.1988.tb02788.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Wu J., Zhou T., He J., Mountz J. D. Autoimmune disease in mice due to integration of an endogenous retrovirus in an apoptosis gene. J Exp Med. 1993 Aug 1;178(2):461–468. doi: 10.1084/jem.178.2.461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Wu J., Zhou T., Zhang J., He J., Gause W. C., Mountz J. D. Correction of accelerated autoimmune disease by early replacement of the mutated lpr gene with the normal Fas apoptosis gene in the T cells of transgenic MRL-lpr/lpr mice. Proc Natl Acad Sci U S A. 1994 Mar 15;91(6):2344–2348. doi: 10.1073/pnas.91.6.2344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Wyllie A. H., Arends M. J., Morris R. G., Walker S. W., Evan G. The apoptosis endonuclease and its regulation. Semin Immunol. 1992 Dec;4(6):389–397. [PubMed] [Google Scholar]
  74. Yin Y., Tainsky M. A., Bischoff F. Z., Strong L. C., Wahl G. M. Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell. 1992 Sep 18;70(6):937–948. doi: 10.1016/0092-8674(92)90244-7. [DOI] [PubMed] [Google Scholar]
  75. Yonehara S., Ishii A., Yonehara M. A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med. 1989 May 1;169(5):1747–1756. doi: 10.1084/jem.169.5.1747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. 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]
  77. Zambetti G. P., Bargonetti J., Walker K., Prives C., Levine A. J. Wild-type p53 mediates positive regulation of gene expression through a specific DNA sequence element. Genes Dev. 1992 Jul;6(7):1143–1152. doi: 10.1101/gad.6.7.1143. [DOI] [PubMed] [Google Scholar]
  78. Zhang W. W., Fang X., Branch C. D., Mazur W., French B. A., Roth J. A. Generation and identification of recombinant adenovirus by liposome-mediated transfection and PCR analysis. Biotechniques. 1993 Nov;15(5):868–872. [PubMed] [Google Scholar]
  79. Zhang W., Funk W. D., Wright W. E., Shay J. W., Deisseroth A. B. Novel DNA binding of p53 mutants and their role in transcriptional activation. Oncogene. 1993 Sep;8(9):2555–2559. [PubMed] [Google Scholar]
  80. Zhang W., Guo X. Y., Hu G. Y., Liu W. B., Shay J. W., Deisseroth A. B. A temperature-sensitive mutant of human p53. EMBO J. 1994 Jun 1;13(11):2535–2544. doi: 10.1002/j.1460-2075.1994.tb06543.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Zhang W., Shay J. W., Deisseroth A. Inactive p53 mutants may enhance the transcriptional activity of wild-type p53. Cancer Res. 1993 Oct 15;53(20):4772–4775. [PubMed] [Google Scholar]
  82. el-Deiry W. S., Kern S. E., Pietenpol J. A., Kinzler K. W., Vogelstein B. Definition of a consensus binding site for p53. Nat Genet. 1992 Apr;1(1):45–49. doi: 10.1038/ng0492-45. [DOI] [PubMed] [Google Scholar]
  83. el-Deiry W. S., Tokino T., Velculescu V. E., Levy D. B., Parsons R., Trent J. M., Lin D., Mercer W. E., Kinzler K. W., Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell. 1993 Nov 19;75(4):817–825. doi: 10.1016/0092-8674(93)90500-p. [DOI] [PubMed] [Google Scholar]

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

RESOURCES