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J Mol Biol. 1998 Aug 14;281(2):205-9.

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

Author information

1
Oncology Department, Novartis, CH-4002 Basel, Switzerland. patrick.chen@pharma.novartis.com

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.

PMID:
9698540
DOI:
10.1006/jmbi.1998.1897
[Indexed for MEDLINE]

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