The Prolonged Half-Life of the p53 Missense Variant R248Q Promotes Accumulation and Heterotetramer Formation with Wild-Type p53 to Exert the Dominant-Negative Effect

Abstract excerpt

Missense mutants of p53, such as the frequent hotspot variant R248Q, exert a dominant-negative effect (DNE) on wild-type (WT) p53 in cancer cells with monoallelic TP53 mutations. However, the precise functional and molecular mechanisms of the DNE have remained elusive due to a lack of appropriate model systems. In this study, we developed a variety of model systems, including CRISPR-edited human isogenic cell...

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