How do I kill thee? Let me count the ways: p53 regulates PARP-1 dependent necrosis

Authors

  • Rana Elkholi,

    1. Icahn School of Medicine at Mount Sinai, Department of Oncological Sciences, New York, NY, USA
    2. Icahn School of Medicine at Mount Sinai, The Tisch Cancer Institute, New York, NY, USA
    3. Icahn School of Medicine at Mount Sinai, The Graduate School of Biomedical Sciences, New York, NY, USA
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  • Jerry E. Chipuk

    Corresponding author
    1. Icahn School of Medicine at Mount Sinai, Department of Oncological Sciences, New York, NY, USA
    2. Icahn School of Medicine at Mount Sinai, The Tisch Cancer Institute, New York, NY, USA
    3. Icahn School of Medicine at Mount Sinai, The Graduate School of Biomedical Sciences, New York, NY, USA
    4. Icahn School of Medicine at Mount Sinai, Department of Dermatology, New York, NY, USA
    5. Icahn School of Medicine at Mount Sinai, The Metabolism Institute, New York, NY, USA
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Abstract

Understanding the impact of the p53 tumor suppressor pathway on the regulation of genome integrity, cancer development, and cancer treatment has intrigued scientists and clinicians for decades. It appears that the p53 pathway is a central node for nearly all cell stress responses, including: gene expression, DNA repair, cell cycle arrest, metabolic adjustments, apoptosis, and senescence. In the past decade, it has become increasingly clear that p53 function is directly regulated by poly(ADP-ribose) polymerase-1 (PARP-1), a nuclear enzyme involved in DNA repair signaling. Here, we will discuss the impact of PARP-1 on p53 function, along with a recently described novel role for the reciprocal regulation of p53 regulated, PARP-1 dependent necrosis following DNA damage.

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