In vitro analysis of the dominant negative effect of p53 mutants

Missense mutations of the p53 tumour suppressor gene induce the formation of proteins with an altered affinity for DNA. These mutant proteins have either a wild-type or a mutant conformation. It has been established that, on association with wild-type protein, molecules with mutant conformation can...

Full description

Saved in:
Bibliographic Details
Published in:Journal of molecular biology 1998-08, Vol.281 (2), p.205-209
Main Author: Chene, P
Format: Article
Language:English
Subjects:
Binding Sites
DNA - metabolism
DNA binding
dominant negative
Genes, Dominant - physiology
Genes, p53 - genetics
Humans
Mutation - physiology
Oligodeoxyribonucleotides
oligomerisation
p53
p53 mutants
Protein Binding
Protein Conformation
Tumor Suppressor Protein p53 - chemistry
Tumor Suppressor Protein p53 - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Missense mutations of the p53 tumour suppressor gene induce the formation of proteins with an altered affinity for DNA. These mutant proteins have either a wild-type or a mutant conformation. It has been established that, on association with wild-type protein, molecules with mutant conformation can drive the wild-type p53 into a mutant conformation. It is shown here that mutant proteins with a wild-type conformation can also inactivate wild-type p53 upon oligomerisation. The dominant negative activity of these mutants depends on their ability to bind to DNA. The less a mutant protein binds to DNA, the more it is dominant negative. Their dominant negative activity is also dependent on the DNA-binding site. The binding of wild-type to a low-affinity DNA element is more easily inactivated by a dominant negative mutant than its binding to a high-affinity DNA-binding site.
ISSN:0022-2836
1089-8638
DOI:10.1006/jmbi.1998.1897