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Functional Properties of p53 Mutant Proteins


The majority of TP53 mutations are missense mutations that accumulate in cancer and are often retained in distant metastasis. This suggests that mutation does more than a loss of function. Indeed, several properties have been ascribed to mutant proteins in addition to a loss of function. These includes dominant-negative effects over wild-type p53 and/or acquisition of new properties (gain-of-function). However, these properties differ from one p53 mutant protein to another.

The information available in the "Function" module of the IARC TP53 Database corresponds to literature data on the functional activities of p53 mutant proteins. Publications that report functional activities of mutant proteins based on (1) transfection and overexpression of p53 mutant proteins in human cells and (2) standardised yeast assays have been included.
Two datasets are available:

(1) Data generated in human or yeast cells on small series of mutants where functional activities or properties of mutant proteins have been grouped into five categories: (1) retained wild-type activity, (2) loss of function, (3) gain of function, (4) dominant-negative effect, (5) temperature sensitivity. Data are compiled in a table that provides information on the experimental system used, the reference from which the information has been extracted and the results of the functional tests performed;

(2) Data courteously provided by Chikashi Ishioka that include transactivation activities of 2314 mutants on 8 p53 response-elements (p53-RE) measured in yeast assays, transactivation activities of 185 mutants on 6 p53-RE measured in Saos-2 cells, apoptotic activities of 183 mutants measured in Saos-2 cells, and oligomerization capacity of 183 mutants measured in yeast assays (Kato et al., Kakudo et al., and Kawaguchi et al.)

Dataset (1) Dataset (2)
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A list of p53-RE used in these assays is available here.