DOI: 10.1126/science.274.5289.948. Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain

Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain

10.1126/science.274.5289.948

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The MDM2 oncoprotein is a cellular inhibitor of the p53 tumor suppressor in that it can bind the transactivation domain of p53 and downregulate its ability to activate transcription. In certain cancers, MDM2 amplification is a common event and contributes to the inactivation of p53. The crystal structure of the 109-residue amino-terminal domain of MDM2 bound to a 15-residue transactivation domain peptide of p53 revealed that MDM2 has a deep hydrophobic cleft on which the p53 peptide binds as an amphipathic α helix. The interface relies on the steric complementarity between the MDM2 cleft and the hydrophobic face of the p53 α helix and, in particular, on a triad of p53 amino acids—Phe 19 , Trp 23 , and Leu 26 —which insert deep into the MDM2 cleft. These same p53 residues are also involved in transactivation, supporting the hypothesis that MDM2 inactivates p53 by concealing its transactivation domain. The structure also suggests that the amphipathic α helix may be a common structural motif in the binding of a diverse family of transactivation factors to the TATA-binding protein-associated factors.

Bibliography

Kussie, P. H., Gorina, S., Marechal, V., Elenbaas, B., Moreau, J., Levine, A. J., & Pavletich, N. P. (1996). Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain. Science, 274(5289), 948â953.

Authors 7

Paul H. Kussie (first)
Svetlana Gorina (additional)
Vincent Marechal (additional)
Brian Elenbaas (additional)
Jacque Moreau (additional)
Arnold J. Levine (additional)
Nikola P. Pavletich (additional)

References 74 Referenced 1,847

Livingstone L. R., et al., Cell 70, 923 (1992); (10.1016/0092-8674(92)90243-6) / Cell by Livingstone L. R. (1992)
Yin Y. Tainsky M. A. Bischoff F. Z. Strong L. C. Wahl G. M. ibid. p. 937;
10.1016/0092-8674(92)90593-2
10.1126/science.7871434
Symonds H., et al., Cell 78, 703 (1994); (10.1016/0092-8674(94)90534-7) / Cell by Symonds H. (1994)
Caelles C., Heimberg A., Karin M., Nature 370, 220 (1994); (10.1038/370220a0) / Nature by Caelles C. (1994)
Wu X., Levine A. J., Proc. Natl. Acad. Sci. U.S.A. 91, 3602 (1994); (10.1073/pnas.91.9.3602) / Proc. Natl. Acad. Sci. U.S.A. by Wu X. (1994)
10.1126/science.8091232
Sabbatini P., Lin J., Levine A. J., White E., Genes Dev. 9, 2184 (1995). (10.1101/gad.9.17.2184) / Genes Dev. by Sabbatini P. (1995)
Levine A. J., Momand J., Finlay C. A., Nature 351, 453 (1991); (10.1038/351453a0) / Nature by Levine A. J. (1991)
Vogelstein B., Kinzer K. W., Cell 70, 523 (1992); (10.1016/0092-8674(92)90421-8) / Cell by Vogelstein B. (1992)
10.1101/gad.10.9.1054
Greenblatt M. S., Bennett W. P., Hollstein M., Harris C. C., Cancer Res. 54, 4855 (1994). / Cancer Res. by Greenblatt M. S. (1994)
Cahilly-Snyder L., Yang-Feng T., Francke U., George D. L., Somat. Cell Mol. Genet. 13, 235 (1987). (10.1007/BF01535205) / Somat. Cell Mol. Genet. by Cahilly-Snyder L. (1987)
10.1016/0092-8674(92)90644-R
Oliner J. D., Kinzler K. W., Meltzer P. S., George D. L., Vogelstein B., Nature 358, 80 (1992). (10.1038/358080a0) / Nature by Oliner J. D. (1992)
Bargonetti J. P., Friedman N., Kern S. E., Vogelstein B., Prives C., Cell 65, 1083 (1991); (10.1016/0092-8674(91)90560-L) / Cell by Bargonetti J. P. (1991)
10.1126/science.2047879
El-Deiry W. S., Kinzler S. E., Pietenpol J. A., Kinzler K. W., Vogelstein B., Nature Genet. 1, 45 (1992). (10.1038/ng0492-45) / Nature Genet. by El-Deiry W. S. (1992)
10.1126/science.2144363
Raycroft L. Wu H. Lozano G. ibid. p. 1049;
Farmer G., et al., Nature 358, 83 (1992); (10.1038/358083a0) / Nature by Farmer G. (1992)
10.1126/science.256.5058.827
Pietenpol J. A., et al., Proc. Natl. Acad. Sci. U.S.A. 91, 1998 (1994). (10.1073/pnas.91.6.1998) / Proc. Natl. Acad. Sci. U.S.A. by Pietenpol J. A. (1994)
Wu X., Bayle J. H., Olson D., Levine A. J., Genes Dev. 7, 1126 (1993). (10.1101/gad.7.7a.1126) / Genes Dev. by Wu X. (1993)
Oliner J. D., et al., Nature 362, 857 (1993). (10.1038/362857a0) / Nature by Oliner J. D. (1993)
de Oca Luna R. M., Wagner D. S., Lozano G., ibid. 378, 203 (1995); / ibid. by de Oca Luna R. M. (1995)
Jones S. N. Roe A. E. Donehower L. A. Bradley A. ibid. p. 206.
Leach F. S., et al., Cancer Res. 53, 2231 (1993); / Cancer Res. by Leach F. S. (1993)
Cordon-Cardo C., et al., ibid. 54, 794 (1994). / ibid. by Cordon-Cardo C. (1994)
Reifenberger G., Lu L., Ichimura K., Schmidt E. E., Collins V. P., ibid. 53, 2736 (1993). / ibid. by Reifenberger G. (1993)
Bueso-Ramos C. E., Yun Y., deLeon E., McCowm P., Stass S., Albitar M., Blood 82, 2617 (1993). (10.1182/blood.V82.9.2617.2617) / Blood by Bueso-Ramos C. E. (1993)
Shibagaki I., et al., Clin. Cancer Res. 1, 769 (1995). / Clin. Cancer Res. by Shibagaki I. (1995)
Marchetti A., et al., J. Pathol. 175, 31 (1995). (10.1002/path.1711750106) / J. Pathol. by Marchetti A. (1995)
Fakharzadeh S. S., Trusko S. P., George D. L., EMBO J. 10, 1565 (1991). (10.1002/j.1460-2075.1991.tb07676.x) / EMBO J. by Fakharzadeh S. S. (1991)
Finlay C. A., Mol. Cell. Biol. 13, 301 (1993). / Mol. Cell. Biol. by Finlay C. A. (1993)
Chen J. Marechal V. Levine A. J. ibid. p. 4107 (1993). (10.1128/mcb.13.7.4107-4114.1993)
10.1126/science.8023157
Lee W., et al. Nature Struct. Biol. 1, 877 (1994); (10.1038/nsb1294-877) / et al. Nature Struct. Biol. by Lee W. (1994)
10.1126/science.7878469
10.1101/gad.8.10.1235
Picksley S. M., Vojtesek B., Sparks A., Lane D. P., Oncogene 9, 2523 (1994). / Oncogene by Picksley S. M. (1994)
Marechal V. et al. in preparation.
10.1126/science.7809597
Lu H., Levine A. J., Proc. Natl. Acad. Sci. U.S.A. 92, 5154 (1995). (10.1073/pnas.92.11.5154) / Proc. Natl. Acad. Sci. U.S.A. by Lu H. (1995)
Pavletich N. P., Chambers K. A., Pabo C. O., Genes Dev. 7, 2556 (1993). (10.1101/gad.7.12b.2556) / Genes Dev. by Pavletich N. P. (1993)
Martin K., et al., Nature 375, 691 (1995). (10.1038/375691a0) / Nature by Martin K. (1995)
Xiao Z.-X. et al. ibid. p. 694.
Bjorkman P. J., et al., ibid. 329, 506 (1987). / ibid. by Bjorkman P. J. (1987)
Brown J. H., et al., ibid. 364, 33 (1993). / ibid. by Brown J. H. (1993)
Wilson I. A., Ghiara J. B., Stanfield R. L., Res. Immunol. 145, 73 (1994). (10.1016/S0923-2494(94)80049-9) / Res. Immunol. by Wilson I. A. (1994)
Stanfield R. L., Wilson I. A., Curr. Opinion Struct. Biol. 5, 103 (1995). (10.1016/0959-440X(95)80015-S) / Curr. Opinion Struct. Biol. by Stanfield R. L. (1995)
10.1126/science.1519061
10.1016/0092-8674(95)90406-9
Chang J., Kim D., Lee S. W., Choi K. Y., Sung Y. C., J. Biol. Chem. 270, 25014 (1995). (10.1074/jbc.270.42.25014) / J. Biol. Chem. by Chang J. (1995)
Gooodrich J. A., Tjian R., Curr. Opinion Cell Biol. 6, 403 (1994); (10.1016/0955-0674(94)90033-7) / Curr. Opinion Cell Biol. by Gooodrich J. A. (1994)
Burley S. K., Roeder R. G., Annu. Rev. Biochem. 65, 769 (1995). (10.1146/annurev.bi.65.070196.004005) / Annu. Rev. Biochem. by Burley S. K. (1995)
10.1126/science.1846049
Schmitz M. L., et al., J. Biol. Chem. 269, 25613 (1994); (10.1016/S0021-9258(18)47294-8) / J. Biol. Chem. by Schmitz M. L. (1994)
Triezenberg S. J., Curr. Opinion Genet. Dev. 5, 190 (1995); (10.1016/0959-437X(95)80007-7) / Curr. Opinion Genet. Dev. by Triezenberg S. J. (1995)
Massari M. E., Jennings P. A., Murre C., Mol. Cell. Biol. 16, 121 (1996). (10.1128/MCB.16.1.121) / Mol. Cell. Biol. by Massari M. E. (1996)
Reiger J. L., Shen F., Triezenberg S. J., Proc. Natl. Acad. Sci. U.S.A. 90, 883 (1993); (10.1073/pnas.90.3.883) / Proc. Natl. Acad. Sci. U.S.A. by Reiger J. L. (1993)
Blair W. S., Bogerd H. P., Cullen B. R., J. Virol. 68, 3803 (1994); (10.1128/jvi.68.6.3803-3808.1994) / J. Virol. by Blair W. S. (1994)
Blair W. S., Bogerd H. P., Madore S. J., Cullen B. R., Mol. Cell. Biol. 14, 7226 (1994); / Mol. Cell. Biol. by Blair W. S. (1994)
Tanaka M., Herr W., ibid. 14, 6056 (1994); / ibid. by Tanaka M. (1994)
Gill G., Pascal E., Tseng Z. H., Tjian R., Proc. Natl. Acad. Sci. U.S.A. 91, 192 (1994). (10.1073/pnas.91.1.192) / Proc. Natl. Acad. Sci. U.S.A. by Gill G. (1994)
Xialoing X., et al., Nature 380, 316 (1996). (10.1038/380316a0) / Nature by Xialoing X. (1996)
Zhang K. Y. J., Acta Crystallogr. D49, 213 (1993). / Acta Crystallogr. by Zhang K. Y. J. (1993)
10.1107/S0108767390010224
Brunger A. T., X-PLOR, a system for crystallography and NMR, Version 3.0 Manual (Yale Univ. Press, New Haven, CT1991). / X-PLOR, a system for crystallography and NMR, Version 3.0 Manual by Brunger A. T. (1991)
Tonrud D. E., Ten Eyck L. F., Matthews B. W., Acta Crystallogr. A43, 489 (1987). (10.1107/S0108767387099124) / Acta Crystallogr. by Tonrud D. E. (1987)
10.1107/S0021889891004399
Merrit E. A., Murphy M. E., Acta Crystallogr. D50, 869 (1994). / Acta Crystallogr. by Merrit E. A. (1994)
10.1002/prot.340110407

Dates

Type	When
Created	23 years ago (July 27, 2002, 5:50 a.m.)
Deposited	1 year ago (Aug. 7, 2024, 7:37 a.m.)
Indexed	1 week, 2 days ago (Aug. 12, 2025, 5:37 p.m.)
Issued	28 years, 9 months ago (Nov. 8, 1996)
Published	28 years, 9 months ago (Nov. 8, 1996)
Published Print	28 years, 9 months ago (Nov. 8, 1996)

Funders 0

None

BibTeX

@article{Kussie_1996, title={Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain}, volume={274}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.274.5289.948}, DOI={10.1126/science.274.5289.948}, number={5289}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Kussie, Paul H. and Gorina, Svetlana and Marechal, Vincent and Elenbaas, Brian and Moreau, Jacque and Levine, Arnold J. and Pavletich, Nikola P.}, year={1996}, month=nov, pages={948–953} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        12
      ]
    ],
    "date-time": "2025-08-12T21:37:34Z",
    "timestamp": 1755034654258
  },
  "reference-count": 74,
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "issue": "5289",
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        1996,
        11,
        8
      ]
    ]
  },
  "abstract": "<jats:p>\n            The MDM2 oncoprotein is a cellular inhibitor of the p53 tumor suppressor in that it can bind the transactivation domain of p53 and downregulate its ability to activate transcription. In certain cancers, MDM2 amplification is a common event and contributes to the inactivation of p53. The crystal structure of the 109-residue amino-terminal domain of MDM2 bound to a 15-residue transactivation domain peptide of p53 revealed that MDM2 has a deep hydrophobic cleft on which the p53 peptide binds as an amphipathic \u03b1 helix. The interface relies on the steric complementarity between the MDM2 cleft and the hydrophobic face of the p53 \u03b1 helix and, in particular, on a triad of p53 amino acids\u2014Phe\n            <jats:sup>19</jats:sup>\n            , Trp\n            <jats:sup>23</jats:sup>\n            , and Leu\n            <jats:sup>26</jats:sup>\n            \u2014which insert deep into the MDM2 cleft. These same p53 residues are also involved in transactivation, supporting the hypothesis that MDM2 inactivates p53 by concealing its transactivation domain. The structure also suggests that the amphipathic \u03b1 helix may be a common structural motif in the binding of a diverse family of transactivation factors to the TATA-binding protein-associated factors.\n          </jats:p>",
  "DOI": "10.1126/science.274.5289.948",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        27
      ]
    ],
    "date-time": "2002-07-27T09:50:14Z",
    "timestamp": 1027763414000
  },
  "page": "948-953",
  "source": "Crossref",
  "is-referenced-by-count": 1847,
  "title": "Structure of the MDM2 Oncoprotein Bound to the p53 Tumor Suppressor Transactivation Domain",
  "prefix": "10.1126",
  "volume": "274",
  "author": [
    {
      "given": "Paul H.",
      "family": "Kussie",
      "sequence": "first",
      "affiliation": [
        {
          "name": "P. H. Kussie, S. Gorina, and N. P. Pavletich are with the Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA."
        }
      ]
    },
    {
      "given": "Svetlana",
      "family": "Gorina",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "P. H. Kussie, S. Gorina, and N. P. Pavletich are with the Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA."
        }
      ]
    },
    {
      "given": "Vincent",
      "family": "Marechal",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "V. Marechal is with the Cervice de Microbiologie, Hopital Rothschild, F-75571, Paris 12, France."
        }
      ]
    },
    {
      "given": "Brian",
      "family": "Elenbaas",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "B. Elenbaas and A. J. Levine are in the Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA."
        }
      ]
    },
    {
      "given": "Jacque",
      "family": "Moreau",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "J. Moreau is at the Institut Jacque Monad, Equipe d'Embryologie, 75251, Paris, France."
        }
      ]
    },
    {
      "given": "Arnold J.",
      "family": "Levine",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "B. Elenbaas and A. J. Levine are in the Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA."
        }
      ]
    },
    {
      "given": "Nikola P.",
      "family": "Pavletich",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "P. H. Kussie, S. Gorina, and N. P. Pavletich are with the Cellular Biochemistry and Biophysics Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA."
        }
      ]
    }
  ],
  "member": "221",
  "reference": [
    {
      "key": "e_1_3_1_2_2",
      "doi-asserted-by": "crossref",
      "first-page": "923",
      "DOI": "10.1016/0092-8674(92)90243-6",
      "volume": "70",
      "author": "Livingstone L. R.",
      "year": "1992",
      "unstructured": "Livingstone L. R., et al., Cell 70, 923 (1992);",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_2_3",
      "unstructured": "Yin Y. Tainsky M. A. Bischoff F. Z. Strong L. C. Wahl G. M. ibid. p. 937;"
    },
    {
      "key": "e_1_3_1_2_4",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(92)90593-2"
    },
    {
      "key": "e_1_3_1_2_5",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7871434"
    },
    {
      "key": "e_1_3_1_3_2",
      "doi-asserted-by": "crossref",
      "first-page": "703",
      "DOI": "10.1016/0092-8674(94)90534-7",
      "volume": "78",
      "author": "Symonds H.",
      "year": "1994",
      "unstructured": "Symonds H., et al., Cell 78, 703 (1994);",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_3_3",
      "doi-asserted-by": "crossref",
      "first-page": "220",
      "DOI": "10.1038/370220a0",
      "volume": "370",
      "author": "Caelles C.",
      "year": "1994",
      "unstructured": "Caelles C., Heimberg A., Karin M., Nature 370, 220 (1994);",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_3_4",
      "doi-asserted-by": "crossref",
      "first-page": "3602",
      "DOI": "10.1073/pnas.91.9.3602",
      "volume": "91",
      "author": "Wu X.",
      "year": "1994",
      "unstructured": "Wu X., Levine A. J., Proc. Natl. Acad. Sci. U.S.A. 91, 3602 (1994);",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_3_5",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.8091232"
    },
    {
      "key": "e_1_3_1_3_6",
      "doi-asserted-by": "crossref",
      "first-page": "2184",
      "DOI": "10.1101/gad.9.17.2184",
      "volume": "9",
      "author": "Sabbatini P.",
      "year": "1995",
      "unstructured": "Sabbatini P., Lin J., Levine A. J., White E., Genes Dev. 9, 2184 (1995).",
      "journal-title": "Genes Dev."
    },
    {
      "key": "e_1_3_1_4_2",
      "doi-asserted-by": "crossref",
      "first-page": "453",
      "DOI": "10.1038/351453a0",
      "volume": "351",
      "author": "Levine A. J.",
      "year": "1991",
      "unstructured": "Levine A. J., Momand J., Finlay C. A., Nature 351, 453 (1991);",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_4_3",
      "doi-asserted-by": "crossref",
      "first-page": "523",
      "DOI": "10.1016/0092-8674(92)90421-8",
      "volume": "70",
      "author": "Vogelstein B.",
      "year": "1992",
      "unstructured": "Vogelstein B., Kinzer K. W., Cell 70, 523 (1992);",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_4_4",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.10.9.1054"
    },
    {
      "key": "e_1_3_1_5_2",
      "first-page": "4855",
      "volume": "54",
      "author": "Greenblatt M. S.",
      "year": "1994",
      "unstructured": "Greenblatt M. S., Bennett W. P., Hollstein M., Harris C. C., Cancer Res. 54, 4855 (1994).",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_3_1_6_2",
      "doi-asserted-by": "crossref",
      "first-page": "235",
      "DOI": "10.1007/BF01535205",
      "volume": "13",
      "author": "Cahilly-Snyder L.",
      "year": "1987",
      "unstructured": "Cahilly-Snyder L., Yang-Feng T., Francke U., George D. L., Somat. Cell Mol. Genet. 13, 235 (1987).",
      "journal-title": "Somat. Cell Mol. Genet."
    },
    {
      "key": "e_1_3_1_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(92)90644-R"
    },
    {
      "key": "e_1_3_1_8_2",
      "doi-asserted-by": "crossref",
      "first-page": "80",
      "DOI": "10.1038/358080a0",
      "volume": "358",
      "author": "Oliner J. D.",
      "year": "1992",
      "unstructured": "Oliner J. D., Kinzler K. W., Meltzer P. S., George D. L., Vogelstein B., Nature 358, 80 (1992).",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_9_2",
      "doi-asserted-by": "crossref",
      "first-page": "1083",
      "DOI": "10.1016/0092-8674(91)90560-L",
      "volume": "65",
      "author": "Bargonetti J. P.",
      "year": "1991",
      "unstructured": "Bargonetti J. P., Friedman N., Kern S. E., Vogelstein B., Prives C., Cell 65, 1083 (1991);",
      "journal-title": "Cell"
    },
    {
      "key": "e_1_3_1_9_3",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2047879"
    },
    {
      "key": "e_1_3_1_9_4",
      "doi-asserted-by": "crossref",
      "first-page": "45",
      "DOI": "10.1038/ng0492-45",
      "volume": "1",
      "author": "El-Deiry W. S.",
      "year": "1992",
      "unstructured": "El-Deiry W. S., Kinzler S. E., Pietenpol J. A., Kinzler K. W., Vogelstein B., Nature Genet. 1, 45 (1992).",
      "journal-title": "Nature Genet."
    },
    {
      "key": "e_1_3_1_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.2144363"
    },
    {
      "key": "e_1_3_1_10_3",
      "unstructured": "Raycroft L. Wu H. Lozano G. ibid. p. 1049;"
    },
    {
      "key": "e_1_3_1_10_4",
      "doi-asserted-by": "crossref",
      "first-page": "83",
      "DOI": "10.1038/358083a0",
      "volume": "358",
      "author": "Farmer G.",
      "year": "1992",
      "unstructured": "Farmer G., et al., Nature 358, 83 (1992);",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_10_5",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.256.5058.827"
    },
    {
      "key": "e_1_3_1_11_2",
      "doi-asserted-by": "crossref",
      "first-page": "1998",
      "DOI": "10.1073/pnas.91.6.1998",
      "volume": "91",
      "author": "Pietenpol J. A.",
      "year": "1994",
      "unstructured": "Pietenpol J. A., et al., Proc. Natl. Acad. Sci. U.S.A. 91, 1998 (1994).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_12_2",
      "doi-asserted-by": "crossref",
      "first-page": "1126",
      "DOI": "10.1101/gad.7.7a.1126",
      "volume": "7",
      "author": "Wu X.",
      "year": "1993",
      "unstructured": "Wu X., Bayle J. H., Olson D., Levine A. J., Genes Dev. 7, 1126 (1993).",
      "journal-title": "Genes Dev."
    },
    {
      "key": "e_1_3_1_13_2",
      "doi-asserted-by": "crossref",
      "first-page": "857",
      "DOI": "10.1038/362857a0",
      "volume": "362",
      "author": "Oliner J. D.",
      "year": "1993",
      "unstructured": "Oliner J. D., et al., Nature 362, 857 (1993).",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_14_2",
      "first-page": "203",
      "volume": "378",
      "author": "de Oca Luna R. M.",
      "year": "1995",
      "unstructured": "de Oca Luna R. M., Wagner D. S., Lozano G., ibid. 378, 203 (1995);",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_14_3",
      "unstructured": "Jones S. N. Roe A. E. Donehower L. A. Bradley A. ibid. p. 206."
    },
    {
      "key": "e_1_3_1_15_2",
      "first-page": "2231",
      "volume": "53",
      "author": "Leach F. S.",
      "year": "1993",
      "unstructured": "Leach F. S., et al., Cancer Res. 53, 2231 (1993);",
      "journal-title": "Cancer Res."
    },
    {
      "key": "e_1_3_1_15_3",
      "first-page": "794",
      "volume": "54",
      "author": "Cordon-Cardo C.",
      "year": "1994",
      "unstructured": "Cordon-Cardo C., et al., ibid. 54, 794 (1994).",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_16_2",
      "first-page": "2736",
      "volume": "53",
      "author": "Reifenberger G.",
      "year": "1993",
      "unstructured": "Reifenberger G., Lu L., Ichimura K., Schmidt E. E., Collins V. P., ibid. 53, 2736 (1993).",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_17_2",
      "doi-asserted-by": "crossref",
      "first-page": "2617",
      "DOI": "10.1182/blood.V82.9.2617.2617",
      "volume": "82",
      "author": "Bueso-Ramos C. E.",
      "year": "1993",
      "unstructured": "Bueso-Ramos C. E., Yun Y., deLeon E., McCowm P., Stass S., Albitar M., Blood 82, 2617 (1993).",
      "journal-title": "Blood"
    },
    {
      "key": "e_1_3_1_18_2",
      "first-page": "769",
      "volume": "1",
      "author": "Shibagaki I.",
      "year": "1995",
      "unstructured": "Shibagaki I., et al., Clin. Cancer Res. 1, 769 (1995).",
      "journal-title": "Clin. Cancer Res."
    },
    {
      "key": "e_1_3_1_19_2",
      "doi-asserted-by": "crossref",
      "first-page": "31",
      "DOI": "10.1002/path.1711750106",
      "volume": "175",
      "author": "Marchetti A.",
      "year": "1995",
      "unstructured": "Marchetti A., et al., J. Pathol. 175, 31 (1995).",
      "journal-title": "J. Pathol."
    },
    {
      "key": "e_1_3_1_20_2",
      "doi-asserted-by": "crossref",
      "first-page": "1565",
      "DOI": "10.1002/j.1460-2075.1991.tb07676.x",
      "volume": "10",
      "author": "Fakharzadeh S. S.",
      "year": "1991",
      "unstructured": "Fakharzadeh S. S., Trusko S. P., George D. L., EMBO J. 10, 1565 (1991).",
      "journal-title": "EMBO J."
    },
    {
      "key": "e_1_3_1_21_2",
      "first-page": "301",
      "volume": "13",
      "author": "Finlay C. A.",
      "year": "1993",
      "unstructured": "Finlay C. A., Mol. Cell. Biol. 13, 301 (1993).",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "e_1_3_1_22_2",
      "doi-asserted-by": "crossref",
      "unstructured": "Chen J. Marechal V. Levine A. J. ibid. p. 4107 (1993).",
      "DOI": "10.1128/mcb.13.7.4107-4114.1993"
    },
    {
      "key": "e_1_3_1_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.8023157"
    },
    {
      "key": "e_1_3_1_24_2",
      "doi-asserted-by": "crossref",
      "first-page": "877",
      "DOI": "10.1038/nsb1294-877",
      "volume": "1",
      "author": "Lee W.",
      "year": "1994",
      "unstructured": "Lee W., et al. Nature Struct. Biol. 1, 877 (1994);",
      "journal-title": "et al. Nature Struct. Biol."
    },
    {
      "key": "e_1_3_1_24_3",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7878469"
    },
    {
      "key": "e_1_3_1_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1101/gad.8.10.1235"
    },
    {
      "key": "e_1_3_1_26_2",
      "first-page": "2523",
      "volume": "9",
      "author": "Picksley S. M.",
      "year": "1994",
      "unstructured": "Picksley S. M., Vojtesek B., Sparks A., Lane D. P., Oncogene 9, 2523 (1994).",
      "journal-title": "Oncogene"
    },
    {
      "key": "e_1_3_1_29_2",
      "unstructured": "Marechal V. et al. in preparation."
    },
    {
      "key": "e_1_3_1_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.7809597"
    },
    {
      "key": "e_1_3_1_31_3",
      "doi-asserted-by": "crossref",
      "first-page": "5154",
      "DOI": "10.1073/pnas.92.11.5154",
      "volume": "92",
      "author": "Lu H.",
      "year": "1995",
      "unstructured": "Lu H., Levine A. J., Proc. Natl. Acad. Sci. U.S.A. 92, 5154 (1995).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_32_2",
      "doi-asserted-by": "crossref",
      "first-page": "2556",
      "DOI": "10.1101/gad.7.12b.2556",
      "volume": "7",
      "author": "Pavletich N. P.",
      "year": "1993",
      "unstructured": "Pavletich N. P., Chambers K. A., Pabo C. O., Genes Dev. 7, 2556 (1993).",
      "journal-title": "Genes Dev."
    },
    {
      "key": "e_1_3_1_33_2",
      "doi-asserted-by": "crossref",
      "first-page": "691",
      "DOI": "10.1038/375691a0",
      "volume": "375",
      "author": "Martin K.",
      "year": "1995",
      "unstructured": "Martin K., et al., Nature 375, 691 (1995).",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_34_2",
      "unstructured": "Xiao Z.-X. et al. ibid. p. 694."
    },
    {
      "key": "e_1_3_1_35_2",
      "first-page": "506",
      "volume": "329",
      "author": "Bjorkman P. J.",
      "year": "1987",
      "unstructured": "Bjorkman P. J., et al., ibid. 329, 506 (1987).",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_36_2",
      "first-page": "33",
      "volume": "364",
      "author": "Brown J. H.",
      "year": "1993",
      "unstructured": "Brown J. H., et al., ibid. 364, 33 (1993).",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_37_2",
      "doi-asserted-by": "crossref",
      "first-page": "73",
      "DOI": "10.1016/S0923-2494(94)80049-9",
      "volume": "145",
      "author": "Wilson I. A.",
      "year": "1994",
      "unstructured": "Wilson I. A., Ghiara J. B., Stanfield R. L., Res. Immunol. 145, 73 (1994).",
      "journal-title": "Res. Immunol."
    },
    {
      "key": "e_1_3_1_38_2",
      "doi-asserted-by": "crossref",
      "first-page": "103",
      "DOI": "10.1016/0959-440X(95)80015-S",
      "volume": "5",
      "author": "Stanfield R. L.",
      "year": "1995",
      "unstructured": "Stanfield R. L., Wilson I. A., Curr. Opinion Struct. Biol. 5, 103 (1995).",
      "journal-title": "Curr. Opinion Struct. Biol."
    },
    {
      "key": "e_1_3_1_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1519061"
    },
    {
      "key": "e_1_3_1_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0092-8674(95)90406-9"
    },
    {
      "key": "e_1_3_1_41_2",
      "doi-asserted-by": "crossref",
      "first-page": "25014",
      "DOI": "10.1074/jbc.270.42.25014",
      "volume": "270",
      "author": "Chang J.",
      "year": "1995",
      "unstructured": "Chang J., Kim D., Lee S. W., Choi K. Y., Sung Y. C., J. Biol. Chem. 270, 25014 (1995).",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "e_1_3_1_42_2",
      "doi-asserted-by": "crossref",
      "first-page": "403",
      "DOI": "10.1016/0955-0674(94)90033-7",
      "volume": "6",
      "author": "Gooodrich J. A.",
      "year": "1994",
      "unstructured": "Gooodrich J. A., Tjian R., Curr. Opinion Cell Biol. 6, 403 (1994);",
      "journal-title": "Curr. Opinion Cell Biol."
    },
    {
      "key": "e_1_3_1_42_3",
      "doi-asserted-by": "crossref",
      "first-page": "769",
      "DOI": "10.1146/annurev.bi.65.070196.004005",
      "volume": "65",
      "author": "Burley S. K.",
      "year": "1995",
      "unstructured": "Burley S. K., Roeder R. G., Annu. Rev. Biochem. 65, 769 (1995).",
      "journal-title": "Annu. Rev. Biochem."
    },
    {
      "key": "e_1_3_1_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1126/science.1846049"
    },
    {
      "key": "e_1_3_1_43_3",
      "doi-asserted-by": "crossref",
      "first-page": "25613",
      "DOI": "10.1016/S0021-9258(18)47294-8",
      "volume": "269",
      "author": "Schmitz M. L.",
      "year": "1994",
      "unstructured": "Schmitz M. L., et al., J. Biol. Chem. 269, 25613 (1994);",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "e_1_3_1_43_4",
      "doi-asserted-by": "crossref",
      "first-page": "190",
      "DOI": "10.1016/0959-437X(95)80007-7",
      "volume": "5",
      "author": "Triezenberg S. J.",
      "year": "1995",
      "unstructured": "Triezenberg S. J., Curr. Opinion Genet. Dev. 5, 190 (1995);",
      "journal-title": "Curr. Opinion Genet. Dev."
    },
    {
      "key": "e_1_3_1_43_5",
      "doi-asserted-by": "crossref",
      "first-page": "121",
      "DOI": "10.1128/MCB.16.1.121",
      "volume": "16",
      "author": "Massari M. E.",
      "year": "1996",
      "unstructured": "Massari M. E., Jennings P. A., Murre C., Mol. Cell. Biol. 16, 121 (1996).",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "e_1_3_1_44_2",
      "doi-asserted-by": "crossref",
      "first-page": "883",
      "DOI": "10.1073/pnas.90.3.883",
      "volume": "90",
      "author": "Reiger J. L.",
      "year": "1993",
      "unstructured": "Reiger J. L., Shen F., Triezenberg S. J., Proc. Natl. Acad. Sci. U.S.A. 90, 883 (1993);",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_44_3",
      "doi-asserted-by": "crossref",
      "first-page": "3803",
      "DOI": "10.1128/jvi.68.6.3803-3808.1994",
      "volume": "68",
      "author": "Blair W. S.",
      "year": "1994",
      "unstructured": "Blair W. S., Bogerd H. P., Cullen B. R., J. Virol. 68, 3803 (1994);",
      "journal-title": "J. Virol."
    },
    {
      "key": "e_1_3_1_44_4",
      "first-page": "7226",
      "volume": "14",
      "author": "Blair W. S.",
      "year": "1994",
      "unstructured": "Blair W. S., Bogerd H. P., Madore S. J., Cullen B. R., Mol. Cell. Biol. 14, 7226 (1994);",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "e_1_3_1_44_5",
      "first-page": "6056",
      "volume": "14",
      "author": "Tanaka M.",
      "year": "1994",
      "unstructured": "Tanaka M., Herr W., ibid. 14, 6056 (1994);",
      "journal-title": "ibid."
    },
    {
      "key": "e_1_3_1_44_6",
      "doi-asserted-by": "crossref",
      "first-page": "192",
      "DOI": "10.1073/pnas.91.1.192",
      "volume": "91",
      "author": "Gill G.",
      "year": "1994",
      "unstructured": "Gill G., Pascal E., Tseng Z. H., Tjian R., Proc. Natl. Acad. Sci. U.S.A. 91, 192 (1994).",
      "journal-title": "Proc. Natl. Acad. Sci. U.S.A."
    },
    {
      "key": "e_1_3_1_45_2",
      "doi-asserted-by": "crossref",
      "first-page": "316",
      "DOI": "10.1038/380316a0",
      "volume": "380",
      "author": "Xialoing X.",
      "year": "1996",
      "unstructured": "Xialoing X., et al., Nature 380, 316 (1996).",
      "journal-title": "Nature"
    },
    {
      "key": "e_1_3_1_47_2",
      "first-page": "213",
      "volume": "49",
      "author": "Zhang K. Y. J.",
      "year": "1993",
      "unstructured": "Zhang K. Y. J., Acta Crystallogr. D49, 213 (1993).",
      "journal-title": "Acta Crystallogr."
    },
    {
      "key": "e_1_3_1_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1107/S0108767390010224"
    },
    {
      "key": "e_1_3_1_49_2",
      "volume-title": "X-PLOR, a system for crystallography and NMR, Version 3.0 Manual",
      "author": "Brunger A. T.",
      "year": "1991",
      "unstructured": "Brunger A. T., X-PLOR, a system for crystallography and NMR, Version 3.0 Manual (Yale Univ. Press, New Haven, CT1991)."
    },
    {
      "key": "e_1_3_1_50_2",
      "doi-asserted-by": "crossref",
      "first-page": "489",
      "DOI": "10.1107/S0108767387099124",
      "volume": "43",
      "author": "Tonrud D. E.",
      "year": "1987",
      "unstructured": "Tonrud D. E., Ten Eyck L. F., Matthews B. W., Acta Crystallogr. A43, 489 (1987).",
      "journal-title": "Acta Crystallogr."
    },
    {
      "key": "e_1_3_1_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1107/S0021889891004399"
    },
    {
      "key": "e_1_3_1_52_2",
      "first-page": "869",
      "volume": "50",
      "author": "Merrit E. A.",
      "year": "1994",
      "unstructured": "Merrit E. A., Murphy M. E., Acta Crystallogr. D50, 869 (1994).",
      "journal-title": "Acta Crystallogr."
    },
    {
      "key": "e_1_3_1_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/prot.340110407"
    }
  ],
  "container-title": "Science",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://www.science.org/doi/pdf/10.1126/science.274.5289.948",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2024,
        8,
        7
      ]
    ],
    "date-time": "2024-08-07T11:37:22Z",
    "timestamp": 1723030642000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://www.science.org/doi/10.1126/science.274.5289.948"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1996,
        11,
        8
      ]
    ]
  },
  "references-count": 74,
  "journal-issue": {
    "issue": "5289",
    "published-print": {
      "date-parts": [
        [
          1996,
          11,
          8
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1126/science.274.5289.948"
  ],
  "URL": "http://dx.doi.org/10.1126/science.274.5289.948",
  "relation": {},
  "ISSN": [
    "0036-8075",
    "1095-9203"
  ],
  "subject": [],
  "container-title-short": "Science",
  "published": {
    "date-parts": [
      [
        1996,
        11,
        8
      ]
    ]
  }
}