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PMID: 7777576 Published · ppublish English Journal Article

The carboxyl-terminal domain of the p53 protein regulates sequence-specific DNA binding through its nonspecific nucleic acid-binding activity.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 92 ·No. 12 ·1995-06-06 ·Pages 5729-33

Bayle JH, Elenbaas B, Levine AJ

Abstract

The murine p53 protein contains two nucleic acid-binding sites, a sequence-specific DNA-binding region localized between amino acid residues 102-290 and a nucleic acid-binding site without sequence specificity that has been localized to residues 364-390. Alternative splicing of mRNA generates two forms of this p53 protein. The normal, or majority, splice form (NSp53) retains its carboxyl-terminal sequence-nonspecific nucleic acid-binding site, which can negatively regulate the sequence-specific DNA-binding site. The alternative splice form of p53 (ASp53) replaces amino acid residues 364-390 with 17 different amino acids. This protein fails to bind nucleic acids nonspecifically and is constitutive for sequence-specific DNA binding. Thus, the binding of nucleic acids at the carboxyl terminus regulates sequence-specific DNA binding by p53. The implications of these findings for the activation of p53 transcriptional activity following DNA damage are discussed.

MeSH Terms
Alternative Splicing Amino Acid Sequence Animals Base Sequence DNA/metabolism DNA-Binding Proteins/metabolism Mice Molecular Sequence Data Oligodeoxyribonucleotides Tumor Suppressor Protein p53/chemistry,genetics,metabolism
Chemicals
DNA-Binding Proteins Oligodeoxyribonucleotides Tumor Suppressor Protein p53 DNA
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bayle J H
Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, NJ 08544, USA.
Elenbaas B
Levine A J
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.92.12.5729
Published
1995-06-06
Pages
5729-33
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC41770
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.92.12.5729 PMC Full Text View journal details
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