Li-Fraumeni Syndrome-Associated Dimer-Forming Mutant p53 Promotes Transactivation-Independent Mitochondrial Cell Death.

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

Cancer discovery（2023）

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Abstract

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.

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Key words

p53,li–fraumeni syndrome–associated,cell death,dimer-forming,transactivation-independent

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