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Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth

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  • Jiajun Zhu

    (Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania
    Epigenetics Program, Perelman School of Medicine, University of Pennsylvania
    Biomedical Graduate Studies, Perelman School of Medicine, University of Pennsylvania)

  • Morgan A. Sammons

    (Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania
    Epigenetics Program, Perelman School of Medicine, University of Pennsylvania)

  • Greg Donahue

    (Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania
    Epigenetics Program, Perelman School of Medicine, University of Pennsylvania)

  • Zhixun Dou

    (Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania
    Epigenetics Program, Perelman School of Medicine, University of Pennsylvania)

  • Masoud Vedadi

    (Structural Genomics Consortium, University of Toronto
    University of Toronto)

  • Matthäus Getlik

    (Drug Discovery Program, Ontario Institute for Cancer Research)

  • Dalia Barsyte-Lovejoy

    (Structural Genomics Consortium, University of Toronto)

  • Rima Al-awar

    (University of Toronto
    Drug Discovery Program, Ontario Institute for Cancer Research)

  • Bryson W. Katona

    (Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania)

  • Ali Shilatifard

    (Feinberg School of Medicine, Northwestern University)

  • Jing Huang

    (Cancer and Stem Cell Epigenetics, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute)

  • Xianxin Hua

    (Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania)

  • Cheryl H. Arrowsmith

    (Structural Genomics Consortium, University of Toronto
    Princess Margaret Cancer Centre, University of Toronto)

  • Shelley L. Berger

    (Cell and Developmental Biology, Perelman School of Medicine, University of Pennsylvania
    Epigenetics Program, Perelman School of Medicine, University of Pennsylvania)

Abstract

A ChIP-seq analysis of the DNA-binding properties of mutant gain-of-function p53 protein compared to wild-type p53 reveals the gain-of-function proteins bind to and activate a distinct set of genes including chromatin modifying enzymes such as the histone methyltransferase MLL; small molecular inhibitors of MLL function may represent a new target for cancers with mutant p53.

Suggested Citation

  • Jiajun Zhu & Morgan A. Sammons & Greg Donahue & Zhixun Dou & Masoud Vedadi & Matthäus Getlik & Dalia Barsyte-Lovejoy & Rima Al-awar & Bryson W. Katona & Ali Shilatifard & Jing Huang & Xianxin Hua & Ch, 2015. "Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth," Nature, Nature, vol. 525(7568), pages 206-211, September.
    • Handle: RePEc:nat:nature:v:525:y:2015:i:7568:d:10.1038_nature15251
    DOI: 10.1038/nature15251
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    Cited by:

    1. An Xu & Mo Liu & Mo-Fan Huang & Yang Zhang & Ruifeng Hu & Julian A. Gingold & Ying Liu & Dandan Zhu & Chian-Shiu Chien & Wei-Chen Wang & Zian Liao & Fei Yuan & Chih-Wei Hsu & Jian Tu & Yao Yu & Taylor, 2023. "Rewired m6A epitranscriptomic networks link mutant p53 to neoplastic transformation," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Derek Wong & Maha Tageldein & Ping Luo & Erik Ensminger & Jeffrey Bruce & Leslie Oldfield & Haifan Gong & Nicholas William Fischer & Brianne Laverty & Vallijah Subasri & Scott Davidson & Reem Khan & A, 2024. "Cell-free DNA from germline TP53 mutation carriers reflect cancer-like fragmentation patterns," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    3. Donglin Ding & Alexandra M. Blee & Jianong Zhang & Yunqian Pan & Nicole A. Becker & L. James Maher & Rafael Jimenez & Liguo Wang & Haojie Huang, 2023. "Gain-of-function mutant p53 together with ERG proto-oncogene drive prostate cancer by beta-catenin activation and pyrimidine synthesis," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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