The human p53 protein

The active form of the human p53 protein is a
tetramer of four identical subunits. Each subunit
has 393 amino acids and five highly conserved
regions, I–V. Region I is part of the transcription-
activation domain; regions II–V
belong to sequence-specific DNA-binding
domains. The carboxyl end beyond amino acid
300 consists of a nonspecific DNA interaction
domain and the tetramerization domain. Proteins
encoded by DNA tumor viruses bind to
p53 and inhibit its activity.Mutations in the p53
gene on human chromosome 17 at p13 (spanning
20 kb of DNA and yielding a 2.8 kb mRNA
transcript from 11 exons) have the greatest effect
when they occur in the conserved regions
II–V in codons 129–146 (exon 4), 171–179
(exon 5), 234–260 (exon 7), and 270–287 (exon
8). Particularly vulnerable are the conserved
amino acids arginine (R) in positions 175, 248,
249, 273, and 282 and glycine (G) in position
245. Mutations occur mainly as missense, resulting
from base-pair substitutions, but some
are insertions and deletions and exert a dominant
negative effect. Knockout mice develop
normally, but develop tumors at a high rate. Activated
benzopyrene induces mutations at codons
175, 248, and 275 in cultured bronchial
epithelial cells.