In vitro analysis of the dominant negative effect of p53 mutants.

Abstract:

: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.

journal_name

J Mol Biol

authors

Chène P

doi

10.1006/jmbi.1998.1897

subject

Has Abstract

pub_date

1998-08-14 00:00:00

pages

205-9

issue

2

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(98)91897-6

journal_volume

281

pub_type

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