DOI: 10.1126/science.2047879. Identification of p53 as a Sequence-Specific DNA-Binding Protein

Identification of p53 as a Sequence-Specific DNA-Binding Protein

10.1126/science.2047879

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

Abstract

The tumor-suppressor gene p53 is altered by missense mutation in numerous human malignancies. However, the biochemical properties of p53 and the effect of mutation on these properties are unclear. A human DNA sequence was identified that binds specifically to wild-type human p53 protein in vitro. As few as 33 base pairs were sufficient to confer specific binding. Certain guanines within this 33-base pair region were critical, as methylation of these guanines or their substitution with thymine-abrogated binding. Human p53 proteins containing either of two missense mutations commonly found in human tumors were unable to bind significantly to this sequence. These data suggest that a function of p53 may be mediated by its ability to bind to specific DNA sequences in the human genome, and that this activity is altered by mutations that occur in human tumors.

Bibliography

Kern, S. E., Kinzler, K. W., Bruskin, A., Jarosz, D., Friedman, P., Prives, C., & Vogelstein, B. (1991). Identification of p53 as a Sequence-Specific DNA-Binding Protein. Science, 252(5013), 1708â1711.

Authors 7

Scott E. Kern (first)
Kenneth W. Kinzler (additional)
Arthur Bruskin (additional)
David Jarosz (additional)
Paula Friedman (additional)
Carol Prives (additional)
Bert Vogelstein (additional)

References 35 Referenced 777

ALITALO, K, HOMOGENEOUSLY STAINING CHROMOSOMAL REGIONS CONTAIN AMPLIFIED COPIES OF AN ABUNDANTLY EXPRESSED CELLULAR ONCOGENE (C-MYC) IN MALIGNANT NEUROENDOCRINE CELLS FROM A HUMAN-COLON CARCINOMA, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 80: 1707 (1983). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES (1983)
ANACHKOVA, B, REPLICATION IN THE AMPLIFIED DIHYDROFOLATE-REDUCTASE DOMAIN IN CHO CELLS MAY INITIATE AT 2 DISTINCT SITES, ONE OF WHICH IS A REPETITIVE SEQUENCE ELEMENT, MOLECULAR AND CELLULAR BIOLOGY 9: 532 (1989). / MOLECULAR AND CELLULAR BIOLOGY (1989)
BAKER, S.J., P53 GENE-MUTATIONS OCCUR IN COMBINATION WITH 17P ALLELIC DELETIONS AS LATE EVENTS IN COLORECTAL TUMORIGENESIS, CANCER RESEARCH 50: 7717 (1990). / CANCER RESEARCH (1990)
10.1126/science.2649981
10.1126/science.2144057
BARTEK, J, GENETIC AND IMMUNOCHEMICAL ANALYSIS OF MUTANT P53 IN HUMAN BREAST-CANCER CELL-LINES, ONCOGENE 5: 893 (1990). / ONCOGENE (1990)
DILLER, L, P53 FUNCTIONS AS A CELL-CYCLE CONTROL PROTEIN IN OSTEOSARCOMAS, MOLECULAR AND CELLULAR BIOLOGY 10: 5772 (1990). / MOLECULAR AND CELLULAR BIOLOGY (1990)
10.1073/pnas.86.22.8763
10.1126/science.2144363
10.1016/0092-8674(89)90045-7
FRIEDMAN, P.N., WILD-TYPE, BUT NOT MUTANT, HUMAN P53 PROTEINS INHIBIT THE REPLICATION ACTIVITIES OF SIMIAN VIRUS-40 LARGE TUMOR-ANTIGEN, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 9275 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
HUBERMAN J COMMUNICATION.
10.1016/0140-6736(90)90801-B
JELINEK, W.R., UBIQUITOUS, INTERSPERSED REPEATED SEQUENCES IN MAMMALIAN GENOMES, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES 77: 1398 (1980). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES (1980)
KERN, S.E., MUTANT P53 PROTEINS BIND DNA ABNORMALLY INVITRO, ONCOGENE 6: 131 (1991). / ONCOGENE (1991)
LANE, D.P., CELLULAR PROTEINS INVOLVED IN SV40 TRANSFORMATION, CELL BIOLOGY INTERNATIONAL REPORTS 7: 513 (1983). (10.1016/0309-1651(83)90154-6) / CELL BIOLOGY INTERNATIONAL REPORTS (1983)
LIN, S, LAC REPRESSOR BINDING TO NON-OPERATOR DNA - DETAILED STUDIES AND A COMPARISON OF EQUILIBRIUM AND RATE COMPETITION METHODS, JOURNAL OF MOLECULAR BIOLOGY 72: 671 (1972). (10.1016/0022-2836(72)90184-2) / JOURNAL OF MOLECULAR BIOLOGY (1972)
10.1016/0092-8674(75)90116-6
LYONS, J, EXPRESSION OF MYCOBACTERIUM-TUBERCULOSIS AND MYCOBACTERIUM-LEPRAE PROTEINS BY VACCINIA VIRUS, INFECTION AND IMMUNITY 58: 4089 (1990). (10.1128/iai.58.12.4089-4098.1990) / INFECTION AND IMMUNITY (1990)
Maniatis, T., Molecular Cloning: A Laboratory Manual: 477 (1982). / Molecular Cloning: A Laboratory Manual (1982)
MCKAY, RDG, BINDING OF A SIMIAN-VIRUS 40-T ANTIGEN-RELATED PROTEIN TO DNA, JOURNAL OF MOLECULAR BIOLOGY 145: 471 (1981). (10.1016/0022-2836(81)90540-4) / JOURNAL OF MOLECULAR BIOLOGY (1981)
10.1073/pnas.87.14.5435
MERCER, W.E., NEGATIVE GROWTH-REGULATION IN A GLIOBLASTOMA TUMOR-CELL LINE THAT CONDITIONALLY EXPRESSES HUMAN WILD-TYPE P53, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 6166 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
MISRA, R, RECOMBINATION MEDIATES PRODUCTION OF AN EXTRACHROMOSOMAL CIRCULAR DNA CONTAINING A TRANSPOSON-LIKE HUMAN ELEMENT, THE-1, NUCLEIC ACIDS RESEARCH 17: 8327 (1989). (10.1093/nar/17.20.8327) / NUCLEIC ACIDS RESEARCH (1989)
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10.1038/342705a0
10.1126/science.2144364
ROMANO, J.W., IDENTIFICATION AND CHARACTERIZATION OF A P53 GENE MUTATION IN A HUMAN OSTEO-SARCOMA CELL-LINE, ONCOGENE 4: 1483 (1989). / ONCOGENE (1989)
STEINMEYER, K, DNA-BINDING PROPERTIES OF MURINE-P53, ONCOGENE 3: 501 (1988). / ONCOGENE (1988)
STRATTON, M.R., MUTATION OF THE P53 GENE IN HUMAN SOFT-TISSUE SARCOMAS - ASSOCIATION WITH ABNORMALITIES OF THE RB1 GENE, ONCOGENE 5: 1297 (1990). / ONCOGENE (1990)
SYLVESTER, J.E., HUMAN RIBOSOMAL DNA - NOVEL SEQUENCE ORGANIZATION IN A 4.5-KB REGION UPSTREAM FROM THE PROMOTER, GENE 84: 193 (1989). (10.1016/0378-1119(89)90155-8) / GENE (1989)
TAKAHASHI, T, IDENTIFICATION OF INTRONIC POINT MUTATIONS AS AN ALTERNATIVE MECHANISM FOR P53 INACTIVATION IN LUNG-CANCER, JOURNAL OF CLINICAL INVESTIGATION 86: 363 (1990). (10.1172/JCI114710) / JOURNAL OF CLINICAL INVESTIGATION (1990)
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VOGELSTEIN, B, CANCER - A DEADLY INHERITANCE, NATURE 348: 681 (1990). (10.1038/348681a0) / NATURE (1990)
10.1126/science.2200124

Dates

Type	When
Created	18 years, 10 months ago (Oct. 5, 2006, 2:10 p.m.)
Deposited	1 year, 7 months ago (Jan. 11, 2024, 5:22 p.m.)
Indexed	2 weeks, 4 days ago (Aug. 6, 2025, 8 a.m.)
Issued	34 years, 2 months ago (June 21, 1991)
Published	34 years, 2 months ago (June 21, 1991)
Published Print	34 years, 2 months ago (June 21, 1991)

Funders 0

None

BibTeX

@article{Kern_1991, title={Identification of p53 as a Sequence-Specific DNA-Binding Protein}, volume={252}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.2047879}, DOI={10.1126/science.2047879}, number={5013}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Kern, Scott E. and Kinzler, Kenneth W. and Bruskin, Arthur and Jarosz, David and Friedman, Paula and Prives, Carol and Vogelstein, Bert}, year={1991}, month=jun, pages={1708–1711} }

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