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p53 mutations in Li-Fraumeni syndrome can cause a gain-of-function in metabolism and affect tumorigenesis

Wednesday, November 06, 2013 — Poster Session I

4:00 p.m. – 6:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • J Zhuang
  • C Lago
  • J Kang
  • PM Hwang


Li-Fraumeni syndrome (LFS) is an autosomal dominant condition caused by germline mutations in TP53 (p53) that predisposes to a variety of cancers. To date approximately 600 different LFS p53 mutations have been found, some of which show gain-of-function activities that promote tumorigenesis. We examined the metabolic effects of LFS mutations in mice and humans as p53 has been shown to regulate mitochondrial respiration. Herein, we report that mutations in p53 can increase mitochondrial biogenesis and respiration with marked exercise capacity improvement. Proteomic and metabolomic screens of the LFS mouse model not only confirmed increased levels of mitochondrial proteins but also revealed decreased levels of factors involved in apoptosis. Human subjects carrying germline p53 mutations demonstrated evidence of increased oxidative phosphorylation capacity and their skeletal muscle cells also showed increased expression of mitochondrial proteins. Our study further shows that the gain-of-function of mutated p53 in metabolism may contribute to tumorigenesis.

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