DOI: 10.1126/science.2537532. The Human Papilloma Virus-16 E7 Oncoprotein Is Able to Bind to the Retinoblastoma Gene Product

The Human Papilloma Virus-16 E7 Oncoprotein Is Able to Bind to the Retinoblastoma Gene Product

10.1126/science.2537532

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

Deletions or mutations of the retinoblastoma gene, RB1, are common features of many tumors and tumor cell lines. Recently, the RB1 gene product, p105-RB, has been shown to form stable protein/protein complexes with the oncoproteins of two DNA tumor viruses, the adenovirus E1A proteins and the simian virus 40 (SV40) large T antigen. Neither of these viruses is thought to be associated with human cancer, but they can cause tumors in rodents. Binding between the RB anti-oncoprotein and the adenovirus or SV40 oncoprotein can be recapitulated in vitro with coimmunoprecipitation mixing assays. These assays have been used to demonstrate that the E7 oncoprotein of the human papilloma virus type-16 can form similar complexes with p105-RB. Human papilloma virus-16 is found associated with approximately 50 percent of cervical carcinomas. These results suggest that these three DNA viruses may utilize similar mechanisms in transformation and implicate RB binding as a possible step in human papilloma virus-associated carcinogenesis.

Bibliography

Dyson, N., Howley, P. M., MÃ¼nger, K., & Harlow, E. (1989). The Human Papilloma Virus-16 E7 Oncoprotein Is Able to Bind to the Retinoblastoma Gene Product. Science, 243(4893), 934â937.

Authors 4

Nicholas Dyson (first)
Peter M. Howley (additional)
Karl Münger (additional)
Ed Harlow (additional)

References 55 Referenced 2,242

10.1128/jvi.61.4.962-971.1987
10.1038/321246a0
10.1146/annurev.ge.20.120186.000401
10.1111/j.1432-1033.1974.tb03599.x
BOSHART, M, EMBO J 3: 1141 (1984). / EMBO J (1984)
10.1128/jvi.45.1.192-199.1983
10.1038/305779a0
10.1056/NEJM198605083141901
10.1002/j.1460-2075.1987.tb02709.x
10.1016/0092-8674(88)90559-4
DURST, M, A PAPILLOMAVIRUS DNA FROM A CERVICAL-CARCINOMA AND ITS PREVALENCE IN CANCER BIOPSY SAMPLES FROM DIFFERENT GEOGRAPHIC REGIONS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 80: 3812 (1983). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES (1983)
Dvson N. Molecular Diagnostics of Human Cancer (1989).
DYSON N unpublished data.
10.1038/323643a0
10.1126/science.2885916
10.1073/pnas.82.18.6216
10.1126/science.2838909
10.1128/jvi.39.3.861-869.1981
10.1128/jvi.55.3.533-546.1985
10.1128/jvi.61.8.2599-2606.1987
10.1101/SQB.1988.053.01.096
10.1126/science.2521957
HOWLEY, P.M., PAPOVAVIRIDAE 2: 245 (1987). / PAPOVAVIRIDAE (1987)
10.1016/0042-6822(86)90366-1
10.1128/jvi.62.2.610-613.1988
KANDA, T, HUMAN PAPILLOMAVIRUS TYPE-16 TRANSFORMATION OF RAT 3Y1 CELLS, JAPANESE JOURNAL OF CANCER RESEARCH 78: 103 (1987). / JAPANESE JOURNAL OF CANCER RESEARCH (1987)
10.1128/jvi.53.2.399-409.1985
10.1073/pnas.68.4.820
10.1038/227680a0
10.1126/science.3388033
10.1126/science.3823889
10.1016/0092-8674(86)90704-X
10.1016/0092-8674(87)90175-9
10.1002/j.1460-2075.1987.tb02426.x
10.1128/jvi.58.3.979-982.1986
10.1016/0092-8674(87)90418-1
MORAN, E, IDENTIFICATION OF SEPARATE DOMAINS IN THE ADENOVIRUS E1A GENE FOR IMMORTALIZATION ACTIVITY AND THE ACTIVATION OF VIRUS EARLY GENES, MOLECULAR AND CELLULAR BIOLOGY 6: 3470 (1986). / MOLECULAR AND CELLULAR BIOLOGY (1986)
10.1038/334168a0
10.1126/science.6320372
10.1016/0092-8674(88)90570-3
10.1002/j.1460-2075.1987.tb02470.x
10.1038/314111a0
10.1128/jvi.61.5.1686-1689.1987
10.1073/pnas.83.13.4680
10.1002/j.1460-2075.1985.tb03934.x
10.1002/j.1460-2075.1988.tb03013.x
10.1002/j.1460-2075.1987.tb02662.x
10.1128/jvi.61.1.134-142.1987
TOOZE J DNA TUMOR VIRUSES (1981).
10.1016/0092-8674(89)90984-7
10.1128/jvi.62.1.257-265.1988
10.1038/334124a0
10.1128/jvi.57.2.572-577.1986
YEE, C.L., AM J PATHOL 119: 3261 (1985). / AM J PATHOL (1985)
ZERLER, B, DIFFERENT FUNCTIONAL DOMAINS OF THE ADENOVIRUS E1A GENE ARE INVOLVED IN REGULATION OF HOST-CELL CYCLE PRODUCTS, MOLECULAR AND CELLULAR BIOLOGY 7: 821 (1987). / MOLECULAR AND CELLULAR BIOLOGY (1987)

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 5:21 p.m.)
Deposited	1 year, 7 months ago (Jan. 12, 2024, 10:15 a.m.)
Indexed	46 minutes ago (Aug. 28, 2025, 8:25 p.m.)
Issued	36 years, 6 months ago (Feb. 17, 1989)
Published	36 years, 6 months ago (Feb. 17, 1989)
Published Print	36 years, 6 months ago (Feb. 17, 1989)

Funders 0

None

BibTeX

@article{Dyson_1989, title={The Human Papilloma Virus-16 E7 Oncoprotein Is Able to Bind to the Retinoblastoma Gene Product}, volume={243}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.2537532}, DOI={10.1126/science.2537532}, number={4893}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Dyson, Nicholas and Howley, Peter M. and Münger, Karl and Harlow, Ed}, year={1989}, month=feb, pages={934–937} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        29
      ]
    ],
    "date-time": "2025-08-29T00:25:06Z",
    "timestamp": 1756427106941
  },
  "reference-count": 55,
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "issue": "4893",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1989,
        2,
        17
      ]
    ]
  },
  "abstract": "<jats:p>Deletions or mutations of the retinoblastoma gene, RB1, are common features of many tumors and tumor cell lines. Recently, the RB1 gene product, p105-RB, has been shown to form stable protein/protein complexes with the oncoproteins of two DNA tumor viruses, the adenovirus E1A proteins and the simian virus 40 (SV40) large T antigen. Neither of these viruses is thought to be associated with human cancer, but they can cause tumors in rodents. Binding between the RB anti-oncoprotein and the adenovirus or SV40 oncoprotein can be recapitulated in vitro with coimmunoprecipitation mixing assays. These assays have been used to demonstrate that the E7 oncoprotein of the human papilloma virus type-16 can form similar complexes with p105-RB. Human papilloma virus-16 is found associated with approximately 50 percent of cervical carcinomas. These results suggest that these three DNA viruses may utilize similar mechanisms in transformation and implicate RB binding as a possible step in human papilloma virus-associated carcinogenesis.</jats:p>",
  "DOI": "10.1126/science.2537532",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2006,
        10,
        5
      ]
    ],
    "date-time": "2006-10-05T21:21:28Z",
    "timestamp": 1160083288000
  },
  "page": "934-937",
  "source": "Crossref",
  "is-referenced-by-count": 2242,
  "title": "The Human Papilloma Virus-16 E7 Oncoprotein Is Able to Bind to the Retinoblastoma Gene Product",
  "prefix": "10.1126",
  "volume": "243",
  "author": [
    {
      "given": "Nicholas",
      "family": "Dyson",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Cold Spring Harbor Laboratory, Cold Spring Harbor, N-Y 11724."
        }
      ]
    },
    {
      "given": "Peter M.",
      "family": "Howley",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, MD 20892"
        }
      ]
    },
    {
      "given": "Karl",
      "family": "M\u00fcnger",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, MD 20892"
        }
      ]
    },
    {
      "given": "Ed",
      "family": "Harlow",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Cold Spring Harbor Laboratory, Cold Spring Harbor, N-Y 11724."
        }
      ]
    }
  ],
  "member": "221",
  "reference": [
    {
      "key": "e_1_2_1_1_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.61.4.962-971.1987"
    },
    {
      "key": "e_1_2_1_2_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/321246a0"
    },
    {
      "key": "e_1_2_1_3_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.ge.20.120186.000401"
    },
    {
      "key": "e_1_2_1_4_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1111/j.1432-1033.1974.tb03599.x"
    },
    {
      "key": "e_1_2_1_5_1",
      "first-page": "1141",
      "volume": "3",
      "year": "1984",
      "unstructured": "BOSHART, M, EMBO J 3: 1141 (1984).",
      "journal-title": "EMBO J"
    },
    {
      "key": "e_1_2_1_6_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.45.1.192-199.1983"
    },
    {
      "key": "e_1_2_1_7_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/305779a0"
    },
    {
      "key": "e_1_2_1_8_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1056/NEJM198605083141901"
    },
    {
      "key": "e_1_2_1_9_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1987.tb02709.x"
    },
    {
      "key": "e_1_2_1_10_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(88)90559-4"
    },
    {
      "key": "e_1_2_1_11_1",
      "first-page": "3812",
      "volume": "80",
      "year": "1983",
      "unstructured": "DURST, M, A PAPILLOMAVIRUS DNA FROM A CERVICAL-CARCINOMA AND ITS PREVALENCE IN CANCER BIOPSY SAMPLES FROM DIFFERENT GEOGRAPHIC REGIONS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 80: 3812 (1983).",
      "journal-title": "PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES"
    },
    {
      "key": "e_1_2_1_12_1",
      "unstructured": "Dvson N. Molecular Diagnostics of Human Cancer (1989)."
    },
    {
      "key": "e_1_2_1_13_1",
      "unstructured": "DYSON N unpublished data."
    },
    {
      "key": "e_1_2_1_14_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/323643a0"
    },
    {
      "key": "e_1_2_1_15_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2885916"
    },
    {
      "key": "e_1_2_1_16_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.82.18.6216"
    },
    {
      "key": "e_1_2_1_17_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2838909"
    },
    {
      "key": "e_1_2_1_18_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.39.3.861-869.1981"
    },
    {
      "key": "e_1_2_1_19_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.55.3.533-546.1985"
    },
    {
      "key": "e_1_2_1_20_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.61.8.2599-2606.1987"
    },
    {
      "key": "e_1_2_1_21_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/SQB.1988.053.01.096"
    },
    {
      "key": "e_1_2_1_22_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2521957"
    },
    {
      "key": "e_1_2_1_23_1",
      "first-page": "245",
      "volume": "2",
      "year": "1987",
      "unstructured": "HOWLEY, P.M., PAPOVAVIRIDAE 2: 245 (1987).",
      "journal-title": "PAPOVAVIRIDAE"
    },
    {
      "key": "e_1_2_1_24_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0042-6822(86)90366-1"
    },
    {
      "key": "e_1_2_1_25_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.62.2.610-613.1988"
    },
    {
      "key": "e_1_2_1_26_1",
      "first-page": "103",
      "volume": "78",
      "year": "1987",
      "unstructured": "KANDA, T, HUMAN PAPILLOMAVIRUS TYPE-16 TRANSFORMATION OF RAT 3Y1 CELLS, JAPANESE JOURNAL OF CANCER RESEARCH 78: 103 (1987).",
      "journal-title": "JAPANESE JOURNAL OF CANCER RESEARCH"
    },
    {
      "key": "e_1_2_1_27_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.53.2.399-409.1985"
    },
    {
      "key": "e_1_2_1_28_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.68.4.820"
    },
    {
      "key": "e_1_2_1_29_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/227680a0"
    },
    {
      "key": "e_1_2_1_30_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.3388033"
    },
    {
      "key": "e_1_2_1_31_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.3823889"
    },
    {
      "key": "e_1_2_1_32_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(86)90704-X"
    },
    {
      "key": "e_1_2_1_33_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(87)90175-9"
    },
    {
      "key": "e_1_2_1_34_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1987.tb02426.x"
    },
    {
      "key": "e_1_2_1_35_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.58.3.979-982.1986"
    },
    {
      "key": "e_1_2_1_36_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(87)90418-1"
    },
    {
      "key": "e_1_2_1_37_1",
      "first-page": "3470",
      "volume": "6",
      "year": "1986",
      "unstructured": "MORAN, E, IDENTIFICATION OF SEPARATE DOMAINS IN THE ADENOVIRUS E1A GENE FOR IMMORTALIZATION ACTIVITY AND THE ACTIVATION OF VIRUS EARLY GENES, MOLECULAR AND CELLULAR BIOLOGY 6: 3470 (1986).",
      "journal-title": "MOLECULAR AND CELLULAR BIOLOGY"
    },
    {
      "key": "e_1_2_1_38_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/334168a0"
    },
    {
      "key": "e_1_2_1_39_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.6320372"
    },
    {
      "key": "e_1_2_1_40_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(88)90570-3"
    },
    {
      "key": "e_1_2_1_41_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1987.tb02470.x"
    },
    {
      "key": "e_1_2_1_42_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/314111a0"
    },
    {
      "key": "e_1_2_1_43_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.61.5.1686-1689.1987"
    },
    {
      "key": "e_1_2_1_44_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.83.13.4680"
    },
    {
      "key": "e_1_2_1_45_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1985.tb03934.x"
    },
    {
      "key": "e_1_2_1_46_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1988.tb03013.x"
    },
    {
      "key": "e_1_2_1_47_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/j.1460-2075.1987.tb02662.x"
    },
    {
      "key": "e_1_2_1_48_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.61.1.134-142.1987"
    },
    {
      "key": "e_1_2_1_49_1",
      "unstructured": "TOOZE J DNA TUMOR VIRUSES (1981)."
    },
    {
      "key": "e_1_2_1_50_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(89)90984-7"
    },
    {
      "key": "e_1_2_1_51_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.62.1.257-265.1988"
    },
    {
      "key": "e_1_2_1_52_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/334124a0"
    },
    {
      "key": "e_1_2_1_53_1",
      "doi-asserted-by": "publisher",
      "DOI": "10.1128/jvi.57.2.572-577.1986"
    },
    {
      "key": "e_1_2_1_54_1",
      "first-page": "3261",
      "volume": "119",
      "year": "1985",
      "unstructured": "YEE, C.L., AM J PATHOL 119: 3261 (1985).",
      "journal-title": "AM J PATHOL"
    },
    {
      "key": "e_1_2_1_55_1",
      "first-page": "821",
      "volume": "7",
      "year": "1987",
      "unstructured": "ZERLER, B, DIFFERENT FUNCTIONAL DOMAINS OF THE ADENOVIRUS E1A GENE ARE INVOLVED IN REGULATION OF HOST-CELL CYCLE PRODUCTS, MOLECULAR AND CELLULAR BIOLOGY 7: 821 (1987).",
      "journal-title": "MOLECULAR AND CELLULAR BIOLOGY"
    }
  ],
  "container-title": "Science",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.science.org/doi/pdf/10.1126/science.2537532",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        1,
        12
      ]
    ],
    "date-time": "2024-01-12T15:15:43Z",
    "timestamp": 1705072543000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.science.org/doi/10.1126/science.2537532"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1989,
        2,
        17
      ]
    ]
  },
  "references-count": 55,
  "journal-issue": {
    "issue": "4893",
    "published-print": {
      "date-parts": [
        [
          1989,
          2,
          17
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1126/science.2537532"
  ],
  "URL": "http://dx.doi.org/10.1126/science.2537532",
  "relation": {},
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        1989,
        2,
        17
      ]
    ]
  }
}