DOI: 10.1126/science.8091232. Mediation of c-Myc-Induced Apoptosis by p53

Mediation of c-Myc-Induced Apoptosis by p53

10.1126/science.8091232

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The cellular proto-oncogene c- myc is involved in cell proliferation and transformation but is also implicated in the induction of programmed cell death (apoptosis). The same characteristics have been described for the tumor suppressor gene p53 , the most commonly mutated gene in human cancer. In quiescent mouse fibroblasts expressing wild-type p53 protein, activation of c-Myc was found to induce apoptosis and cell cycle reentry, preceded by stabilization of p53. In contrast, in quiescent p53-null fibroblasts, activation of c-Myc induced cell cycle reentry but not apoptosis. These results suggest that p53 mediates apoptosis as a safeguard mechanism to prevent cell proliferation induced by oncogene activation.

Bibliography

Hermeking, H., & Eick, D. (1994). Mediation of c-Myc-Induced Apoptosis by p53. Science, 265(5181), 2091â2093.

Authors 2

Heiko Hermeking (first)
Dirk Eick (additional)

References 26 Referenced 564

ASKEW, D.S., CONSTITUTIVE C-MYC EXPRESSION IN AN IL-3-DEPENDENT MYELOID CELL-LINE SUPPRESSES CELL-CYCLE ARREST AND ACCELERATES APOPTOSIS, ONCOGENE 6: 1915 (1991). / ONCOGENE (1991)
BELLOFERNANDEZ, C, THE ORNITHINE DECARBOXYLASE GENE IS A TRANSCRIPTIONAL TARGET OF C-MYC, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 90: 7804 (1993). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1993)
BENVENISTY, N, AN EMBRYONICALLY EXPRESSED GENE IS A TARGET FOR C-MYC REGULATION VIA THE C-MYC-BINDING SEQUENCE, GENES & DEVELOPMENT 6: 2513 (1992). (10.1101/gad.6.12b.2513) / GENES & DEVELOPMENT (1992)
DEBBAS, M, WILD-TYPE P53 MEDIATES APOPTOSIS BY E1A, WHICH IS INHIBITED BY E1B, GENES & DEVELOPMENT 7: 546 (1993). (10.1101/gad.7.4.546) / GENES & DEVELOPMENT (1993)
DONEHOWER, L.A., THE TUMOR-SUPPRESSOR P53, BIOCHIMICA ET BIOPHYSICA ACTA 1155: 181 (1993). / BIOCHIMICA ET BIOPHYSICA ACTA (1993)
10.1038/356215a0
EILERS, M, THE MYC PROTEIN ACTIVATES TRANSCRIPTION OF THE ALPHA-PROTHYMOSIN GENE, EMBO JOURNAL 10: 133 (1991). (10.1002/j.1460-2075.1991.tb07929.x) / EMBO JOURNAL (1991)
10.1016/0092-8674(93)90500-P
EVAN, G.I., INDUCTION OF APOPTOSIS IN FIBROBLASTS BY C-MYC PROTEIN, CELL 69: 119 (1992). (10.1016/0092-8674(92)90123-T) / CELL (1992)
EVAN, G.I., CURR OPIN GENE DEV 3: 44 (1993). (10.1016/S0959-437X(05)80339-9) / CURR OPIN GENE DEV (1993)
GANNON, J.V., ACTIVATING MUTATIONS IN P53 PRODUCE A COMMON CONFORMATIONAL EFFECT - A MONOCLONAL-ANTIBODY SPECIFIC FOR THE MUTANT FORM, EMBO JOURNAL 9: 1595 (1990). (10.1002/j.1460-2075.1990.tb08279.x) / EMBO JOURNAL (1990)
GURNEY, E.G., MONOCLONAL-ANTIBODIES AGAINST SIMIAN VIRUS-40 T-ANTIGENS - EVIDENCE FOR DISTINCT SUBCLASSES OF LARGE T-ANTIGEN AND FOR SIMILARITIES AMONG NON-VIRAL T-ANTIGENS, JOURNAL OF VIROLOGY 34: 752 (1980). (10.1128/jvi.34.3.752-763.1980) / JOURNAL OF VIROLOGY (1980)
HARVEY, M, IN-VITRO GROWTH-CHARACTERISTICS OF EMBRYO FIBROBLASTS ISOLATED FROM P53-DEFICIENT MICE, ONCOGENE 8: 2457 (1993). / ONCOGENE (1993)
Hermeking, H., Proceedings of the National Academy of Sciences of the United States of America 91: 10412 (1994). / Proceedings of the National Academy of Sciences of the United States of America (1994)
HERMEKING H unpublished data.
KASTAN, M.B., PARTICIPATION OF P53 PROTEIN IN THE CELLULAR-RESPONSE TO DNA DAMAGE, CANCER RESEARCH 51: 6304 (1991). / CANCER RESEARCH (1991)
10.1016/0092-8674(92)90593-2
KUMAR, V, LOCALIZATION OF THE ESTRADIOL-BINDING AND PUTATIVE DNA-BINDING DOMAINS OF THE HUMAN ESTROGEN-RECEPTOR, EMBO JOURNAL 5: 2231 (1986). (10.1002/j.1460-2075.1986.tb04489.x) / EMBO JOURNAL (1986)
10.1016/0092-8674(93)90719-7
LOWE, S.W., STABILIZATION OF THE P53 TUMOR SUPPRESSOR IS INDUCED BY ADENOVIRUS-5 E1A AND ACCOMPANIES APOPTOSIS, GENES & DEVELOPMENT 7: 535 (1993). (10.1101/gad.7.4.535) / GENES & DEVELOPMENT (1993)
LU, X, DIFFERENTIAL INDUCTION OF TRANSCRIPTIONALLY ACTIVE P53 FOLLOWING UV OR IONIZING-RADIATION - DEFECTS IN CHROMOSOME INSTABILITY SYNDROMES, CELL 75: 765 (1993). (10.1016/0092-8674(93)90496-D) / CELL (1993)
MARCU, K.B., MYC FUNCTION AND REGULATION, ANNUAL REVIEW OF BIOCHEMISTRY 61: 809 (1992). (10.1146/annurev.bi.61.070192.004113) / ANNUAL REVIEW OF BIOCHEMISTRY (1992)
10.1016/S0959-437X(05)80340-5
REICH, N.C., GROWTH-REGULATION OF A CELLULAR TUMOR-ANTIGEN, P53, IN NONTRANSFORMED CELLS, NATURE 308: 199 (1984). (10.1038/308199a0) / NATURE (1984)
Sambrook J. Molecular Cloning: A Laboratory Manual (1989).
10.1126/science.1378649

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 8:01 p.m.)
Deposited	1 year, 7 months ago (Jan. 14, 2024, 10:53 p.m.)
Indexed	1 day, 2 hours ago (Aug. 31, 2025, 6:27 a.m.)
Issued	30 years, 11 months ago (Sept. 30, 1994)
Published	30 years, 11 months ago (Sept. 30, 1994)
Published Print	30 years, 11 months ago (Sept. 30, 1994)

Funders 0

None

BibTeX

@article{Hermeking_1994, title={Mediation of c-Myc-Induced Apoptosis by p53}, volume={265}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.8091232}, DOI={10.1126/science.8091232}, number={5181}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Hermeking, Heiko and Eick, Dirk}, year={1994}, month=sep, pages={2091–2093} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        31
      ]
    ],
    "date-time": "2025-08-31T10:27:47Z",
    "timestamp": 1756636067470
  },
  "reference-count": 26,
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "issue": "5181",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1994,
        9,
        30
      ]
    ]
  },
  "abstract": "<jats:p>\n            The cellular proto-oncogene c-\n            <jats:italic>myc</jats:italic>\n            is involved in cell proliferation and transformation but is also implicated in the induction of programmed cell death (apoptosis). The same characteristics have been described for the tumor suppressor gene\n            <jats:italic>p53</jats:italic>\n            , the most commonly mutated gene in human cancer. In quiescent mouse fibroblasts expressing wild-type p53 protein, activation of c-Myc was found to induce apoptosis and cell cycle reentry, preceded by stabilization of p53. In contrast, in quiescent p53-null fibroblasts, activation of c-Myc induced cell cycle reentry but not apoptosis. These results suggest that p53 mediates apoptosis as a safeguard mechanism to prevent cell proliferation induced by oncogene activation.\n          </jats:p>",
  "DOI": "10.1126/science.8091232",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2006,
        10,
        6
      ]
    ],
    "date-time": "2006-10-06T00:01:25Z",
    "timestamp": 1160092885000
  },
  "page": "2091-2093",
  "source": "Crossref",
  "is-referenced-by-count": 564,
  "title": "Mediation of c-Myc-Induced Apoptosis by p53",
  "prefix": "10.1126",
  "volume": "265",
  "author": [
    {
      "given": "Heiko",
      "family": "Hermeking",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Institut f\u00fcr Klinische Molekularbiologie und Tumorgenetik Forschungszentrum f\u00fcr Umwelt und Gesundheit, GSF, Munchen, Germany."
        }
      ]
    },
    {
      "given": "Dirk",
      "family": "Eick",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Institut f\u00fcr Klinische Molekularbiologie und Tumorgenetik Forschungszentrum f\u00fcr Umwelt und Gesundheit, GSF, Munchen, Germany."
        }
      ]
    }
  ],
  "member": "221",
  "reference": [
    {
      "key": "e_1_2_1_1_1",
      "first-page": "1915",
      "volume": "6",
      "year": "1991",
      "unstructured": "ASKEW, D.S., CONSTITUTIVE C-MYC EXPRESSION IN AN IL-3-DEPENDENT MYELOID CELL-LINE SUPPRESSES CELL-CYCLE ARREST AND ACCELERATES APOPTOSIS, ONCOGENE 6: 1915 (1991).",
      "journal-title": "ONCOGENE"
    },
    {
      "key": "e_1_2_1_2_1",
      "first-page": "7804",
      "volume": "90",
      "year": "1993",
      "unstructured": "BELLOFERNANDEZ, C, THE ORNITHINE DECARBOXYLASE GENE IS A TRANSCRIPTIONAL TARGET OF C-MYC, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 90: 7804 (1993).",
      "journal-title": "PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA"
    },
    {
      "key": "e_1_2_1_3_1",
      "doi-asserted-by": "crossref",
      "first-page": "2513",
      "DOI": "10.1101/gad.6.12b.2513",
      "volume": "6",
      "year": "1992",
      "unstructured": "BENVENISTY, N, AN EMBRYONICALLY EXPRESSED GENE IS A TARGET FOR C-MYC REGULATION VIA THE C-MYC-BINDING SEQUENCE, GENES & DEVELOPMENT 6: 2513 (1992).",
      "journal-title": "GENES & DEVELOPMENT"
    },
    {
      "key": "e_1_2_1_4_1",
      "doi-asserted-by": "crossref",
      "first-page": "546",
      "DOI": "10.1101/gad.7.4.546",
      "volume": "7",
      "year": "1993",
      "unstructured": "DEBBAS, M, WILD-TYPE P53 MEDIATES APOPTOSIS BY E1A, WHICH IS INHIBITED BY E1B, GENES & DEVELOPMENT 7: 546 (1993).",
      "journal-title": "GENES & DEVELOPMENT"
    },
    {
      "key": "e_1_2_1_5_1",
      "first-page": "181",
      "volume": "1155",
      "year": "1993",
      "unstructured": "DONEHOWER, L.A., THE TUMOR-SUPPRESSOR P53, BIOCHIMICA ET BIOPHYSICA ACTA 1155: 181 (1993).",
      "journal-title": "BIOCHIMICA ET BIOPHYSICA ACTA"
    },
    {
      "key": "e_1_2_1_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/356215a0"
    },
    {
      "key": "e_1_2_1_7_1",
      "doi-asserted-by": "crossref",
      "first-page": "133",
      "DOI": "10.1002/j.1460-2075.1991.tb07929.x",
      "volume": "10",
      "year": "1991",
      "unstructured": "EILERS, M, THE MYC PROTEIN ACTIVATES TRANSCRIPTION OF THE ALPHA-PROTHYMOSIN GENE, EMBO JOURNAL 10: 133 (1991).",
      "journal-title": "EMBO JOURNAL"
    },
    {
      "key": "e_1_2_1_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(93)90500-P"
    },
    {
      "key": "e_1_2_1_9_1",
      "doi-asserted-by": "crossref",
      "first-page": "119",
      "DOI": "10.1016/0092-8674(92)90123-T",
      "volume": "69",
      "year": "1992",
      "unstructured": "EVAN, G.I., INDUCTION OF APOPTOSIS IN FIBROBLASTS BY C-MYC PROTEIN, CELL 69: 119 (1992).",
      "journal-title": "CELL"
    },
    {
      "key": "e_1_2_1_10_1",
      "doi-asserted-by": "crossref",
      "first-page": "44",
      "DOI": "10.1016/S0959-437X(05)80339-9",
      "volume": "3",
      "year": "1993",
      "unstructured": "EVAN, G.I., CURR OPIN GENE DEV 3: 44 (1993).",
      "journal-title": "CURR OPIN GENE DEV"
    },
    {
      "key": "e_1_2_1_11_1",
      "doi-asserted-by": "crossref",
      "first-page": "1595",
      "DOI": "10.1002/j.1460-2075.1990.tb08279.x",
      "volume": "9",
      "year": "1990",
      "unstructured": "GANNON, J.V., ACTIVATING MUTATIONS IN P53 PRODUCE A COMMON CONFORMATIONAL EFFECT - A MONOCLONAL-ANTIBODY SPECIFIC FOR THE MUTANT FORM, EMBO JOURNAL 9: 1595 (1990).",
      "journal-title": "EMBO JOURNAL"
    },
    {
      "key": "e_1_2_1_12_1",
      "doi-asserted-by": "crossref",
      "first-page": "752",
      "DOI": "10.1128/jvi.34.3.752-763.1980",
      "volume": "34",
      "year": "1980",
      "unstructured": "GURNEY, E.G., MONOCLONAL-ANTIBODIES AGAINST SIMIAN VIRUS-40 T-ANTIGENS - EVIDENCE FOR DISTINCT SUBCLASSES OF LARGE T-ANTIGEN AND FOR SIMILARITIES AMONG NON-VIRAL T-ANTIGENS, JOURNAL OF VIROLOGY 34: 752 (1980).",
      "journal-title": "JOURNAL OF VIROLOGY"
    },
    {
      "key": "e_1_2_1_13_1",
      "first-page": "2457",
      "volume": "8",
      "year": "1993",
      "unstructured": "HARVEY, M, IN-VITRO GROWTH-CHARACTERISTICS OF EMBRYO FIBROBLASTS ISOLATED FROM P53-DEFICIENT MICE, ONCOGENE 8: 2457 (1993).",
      "journal-title": "ONCOGENE"
    },
    {
      "key": "e_1_2_1_14_1",
      "first-page": "10412",
      "volume": "91",
      "year": "1994",
      "unstructured": "Hermeking, H., Proceedings of the National Academy of Sciences of the United States of America 91: 10412 (1994).",
      "journal-title": "Proceedings of the National Academy of Sciences of the United States of America"
    },
    {
      "key": "e_1_2_1_15_1",
      "unstructured": "HERMEKING H unpublished data."
    },
    {
      "key": "e_1_2_1_16_1",
      "first-page": "6304",
      "volume": "51",
      "year": "1991",
      "unstructured": "KASTAN, M.B., PARTICIPATION OF P53 PROTEIN IN THE CELLULAR-RESPONSE TO DNA DAMAGE, CANCER RESEARCH 51: 6304 (1991).",
      "journal-title": "CANCER RESEARCH"
    },
    {
      "key": "e_1_2_1_17_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(92)90593-2"
    },
    {
      "key": "e_1_2_1_18_1",
      "doi-asserted-by": "crossref",
      "first-page": "2231",
      "DOI": "10.1002/j.1460-2075.1986.tb04489.x",
      "volume": "5",
      "year": "1986",
      "unstructured": "KUMAR, V, LOCALIZATION OF THE ESTRADIOL-BINDING AND PUTATIVE DNA-BINDING DOMAINS OF THE HUMAN ESTROGEN-RECEPTOR, EMBO JOURNAL 5: 2231 (1986).",
      "journal-title": "EMBO JOURNAL"
    },
    {
      "key": "e_1_2_1_19_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(93)90719-7"
    },
    {
      "key": "e_1_2_1_20_1",
      "doi-asserted-by": "crossref",
      "first-page": "535",
      "DOI": "10.1101/gad.7.4.535",
      "volume": "7",
      "year": "1993",
      "unstructured": "LOWE, S.W., STABILIZATION OF THE P53 TUMOR SUPPRESSOR IS INDUCED BY ADENOVIRUS-5 E1A AND ACCOMPANIES APOPTOSIS, GENES & DEVELOPMENT 7: 535 (1993).",
      "journal-title": "GENES & DEVELOPMENT"
    },
    {
      "key": "e_1_2_1_21_1",
      "doi-asserted-by": "crossref",
      "first-page": "765",
      "DOI": "10.1016/0092-8674(93)90496-D",
      "volume": "75",
      "year": "1993",
      "unstructured": "LU, X, DIFFERENTIAL INDUCTION OF TRANSCRIPTIONALLY ACTIVE P53 FOLLOWING UV OR IONIZING-RADIATION - DEFECTS IN CHROMOSOME INSTABILITY SYNDROMES, CELL 75: 765 (1993).",
      "journal-title": "CELL"
    },
    {
      "key": "e_1_2_1_22_1",
      "doi-asserted-by": "crossref",
      "first-page": "809",
      "DOI": "10.1146/annurev.bi.61.070192.004113",
      "volume": "61",
      "year": "1992",
      "unstructured": "MARCU, K.B., MYC FUNCTION AND REGULATION, ANNUAL REVIEW OF BIOCHEMISTRY 61: 809 (1992).",
      "journal-title": "ANNUAL REVIEW OF BIOCHEMISTRY"
    },
    {
      "key": "e_1_2_1_23_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0959-437X(05)80340-5"
    },
    {
      "key": "e_1_2_1_24_1",
      "doi-asserted-by": "crossref",
      "first-page": "199",
      "DOI": "10.1038/308199a0",
      "volume": "308",
      "year": "1984",
      "unstructured": "REICH, N.C., GROWTH-REGULATION OF A CELLULAR TUMOR-ANTIGEN, P53, IN NONTRANSFORMED CELLS, NATURE 308: 199 (1984).",
      "journal-title": "NATURE"
    },
    {
      "key": "e_1_2_1_25_1",
      "unstructured": "Sambrook J. Molecular Cloning: A Laboratory Manual (1989)."
    },
    {
      "key": "e_1_2_1_26_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1378649"
    }
  ],
  "container-title": "Science",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.science.org/doi/pdf/10.1126/science.8091232",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        15
      ]
    ],
    "date-time": "2024-01-15T03:53:34Z",
    "timestamp": 1705290814000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.science.org/doi/10.1126/science.8091232"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1994,
        9,
        30
      ]
    ]
  },
  "references-count": 26,
  "journal-issue": {
    "issue": "5181",
    "published-print": {
      "date-parts": [
        [
          1994,
          9,
          30
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1126/science.8091232"
  ],
  "URL": "http://dx.doi.org/10.1126/science.8091232",
  "relation": {},
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        1994,
        9,
        30
      ]
    ]
  }
}