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Wamsley JJ, Gary C, Biktasova A, et al. Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner. Oncogenesis. 2017;6(4):e314doi: 10.1038/oncsis.2017.12.
Wamsley, J. J., Gary, C., Biktasova, A., Hajek, M., Bellinger, G., Virk, R., Issaeva, N., & Yarbrough, W. G. (2017). Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner. Oncogenesis, 6(4), e314. https://doi.org/10.1038/oncsis.2017.12
Wamsley, J J, et al. "Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner." Oncogenesis vol. 6,4 (2017): e314. doi: https://doi.org/10.1038/oncsis.2017.12
Wamsley JJ, Gary C, Biktasova A, Hajek M, Bellinger G, Virk R, Issaeva N, Yarbrough WG. Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner. Oncogenesis. 2017 Apr 10;6(4):e314. doi: 10.1038/oncsis.2017.12. PMID: 28394357; PMCID: PMC5520489.
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Oncogenesis. 2017 Apr 10;6(4):e314. doi: 10.1038/oncsis.2017.12.

Loss of LZAP inactivates p53 and regulates sensitivity of cells to DNA damage in a p53-dependent manner.

Oncogenesis

J J Wamsley, C Gary, A Biktasova, M Hajek, G Bellinger, R Virk, N Issaeva, W G Yarbrough

Affiliations

  1. Division of Otolaryngology, Department of Surgery, Yale University School of Medicine, New Haven, CT, USA.
  2. Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA.
  3. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA.

PMID: 28394357 PMCID: PMC5520489 DOI: 10.1038/oncsis.2017.12

Abstract

Chemotherapy and radiation, the two most common cancer therapies, exert their anticancer effects by causing damage to cellular DNA. However, systemic treatment damages DNA not only in cancer, but also in healthy cells, resulting in the progression of serious side effects and limiting efficacy of the treatment. Interestingly, in response to DNA damage, p53 seems to play an opposite role in normal and in the majority of cancer cells-wild-type p53 mediates apoptosis in healthy tissues, attributing to the side effects, whereas mutant p53 often is responsible for acquired cancer resistance to the treatment. Here, we show that leucine zipper-containing ARF-binding protein (LZAP) binds and stabilizes p53. LZAP depletion eliminates p53 protein independently of its mutation status, subsequently protecting wild-type p53 cells from DNA damage-induced cell death, while rendering cells expressing mutant p53 more sensitive to the treatment. In human non-small-cell lung cancer, LZAP levels correlated with p53 levels, suggesting that loss of LZAP may represent a novel mechanism of p53 inactivation in human cancer. Our studies establish LZAP as a p53 regulator and p53-dependent determinative of cell fate in response to DNA damaging treatment.

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