Li-Fraumeni Syndrome-Associated Dimer-Forming Mutant P53 Promotes Transactivation-Independent Mitochondrial Cell Death

Overview

Journal Cancer Discov

Specialty Oncology

Date 2023 Apr 17

PMID 37067901

Authors

Joshua H Choe

Tatsuya Kawase

An Xu

Asja Guzman

Aleksandar Z Obradovic

Ana Maria Low-Calle

Bita Alaghebandan

Ananya Raghavan

Kaitlin Long

Paul M Hwang

Joshua D Schiffman

Yan Zhu

Ruiying Zhao

Dung-Fang Lee

Chen Katz

Carol Prives

Affiliations

Soon will be listed here.

Abstract

Significance: A mutant p53 (A347D), which can only form dimers, is associated with increased cancer susceptibility in LFS individuals. We found that this mutant wields a double-edged sword, driving tumorigenesis through LOF while gaining enhanced apoptogenic activity as a new GOF, thereby yielding a potential vulnerability to select therapeutic approaches. See related commentary by Stieg et al., p. 1046. See related article by Gencel-Augusto et al., p. 1230. This article is highlighted in the In This Issue feature, p. 1027.

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