Identification of p53 as a sequence-specific DNA-binding protein

Scott E Kern, Kenneth W Kinzler, Arthur Bruskin, David Jarosz, Paula Friedman, Carol Prives, Bert Vogelstein

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1708-1711
Number of pages4
JournalScience
Volume252
Issue number5013
StatePublished - Jun 21 1991

Fingerprint

DNA-Binding Proteins
Guanine
Missense Mutation
Base Pairing
Neoplasms
Mutation
Thymine
Human Genome
Tumor Suppressor Genes
Human Activities
Methylation
Proteins

ASJC Scopus subject areas

  • General

Cite this

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), 1708-1711.

Identification of p53 as a sequence-specific DNA-binding protein. / Kern, Scott E; Kinzler, Kenneth W; Bruskin, Arthur; Jarosz, David; Friedman, Paula; Prives, Carol; Vogelstein, Bert.

In: Science, Vol. 252, No. 5013, 21.06.1991, p. 1708-1711.

Research output: Contribution to journalArticle

Kern, SE, Kinzler, KW, Bruskin, A, Jarosz, D, Friedman, P, Prives, C & Vogelstein, B 1991, 'Identification of p53 as a sequence-specific DNA-binding protein', Science, vol. 252, no. 5013, pp. 1708-1711.
Kern SE, Kinzler KW, Bruskin A, Jarosz D, Friedman P, Prives C et al. Identification of p53 as a sequence-specific DNA-binding protein. Science. 1991 Jun 21;252(5013):1708-1711.
Kern, Scott E ; Kinzler, Kenneth W ; Bruskin, Arthur ; Jarosz, David ; Friedman, Paula ; Prives, Carol ; Vogelstein, Bert. / Identification of p53 as a sequence-specific DNA-binding protein. In: Science. 1991 ; Vol. 252, No. 5013. pp. 1708-1711.
@article{49aad62a4be348a4abad2486396a7175,
title = "Identification of p53 as a sequence-specific DNA-binding protein",
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.",
author = "Kern, {Scott E} and Kinzler, {Kenneth W} and Arthur Bruskin and David Jarosz and Paula Friedman and Carol Prives and Bert Vogelstein",
year = "1991",
month = "6",
day = "21",
language = "English (US)",
volume = "252",
pages = "1708--1711",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "5013",

}

TY - JOUR

T1 - Identification of p53 as a sequence-specific DNA-binding protein

AU - Kern, Scott E

AU - Kinzler, Kenneth W

AU - Bruskin, Arthur

AU - Jarosz, David

AU - Friedman, Paula

AU - Prives, Carol

AU - Vogelstein, Bert

PY - 1991/6/21

Y1 - 1991/6/21

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0025815451&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025815451&partnerID=8YFLogxK

M3 - Article

VL - 252

SP - 1708

EP - 1711

JO - Science

JF - Science

SN - 0036-8075

IS - 5013

ER -