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

Science 1991 Jun;252(5013):1708-11

Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21231.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1126/science.2047879DOI Listing
June 1991

Publication Analysis

Top Keywords

human p53
8
human tumors
8
human
7
p53
5
methylation guanines
4
critical methylation
4
guanines substitution
4
region critical
4
substitution thymine-abrogated
4
proteins missense
4
p53 proteins
4
binding human
4
thymine-abrogated binding
4
pair region
4
guanines 33-base
4
base pairs
4
vitro base
4
protein vitro
4
p53 protein
4
pairs sufficient
4

References

(Supplied by CrossRef)

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICABIOLOGICAL SCIENCES 1983

Anachkova et al.
Molecular and Cellular Biology 1989

Baker et al.
Cancer Research 1990

Baker et al.
Science 1989

Baker et al.
Science 1990

Bartek et al.
Oncogene 1990

Diller et al.
Molecular and Cellular Biology 1990

Eliyahu et al.
PNAS 1989

Fields et al.
Science 1990

Finlay et al.
Cell 1989

Friedman et al.
PNAS 1990

Similar Publications