Research ArticleCancer

Tissue-specific regulation of p53 by PKM2 is redox dependent and provides a therapeutic target for anthracycline-induced cardiotoxicity

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Science Translational Medicine  06 Feb 2019:
Vol. 11, Issue 478, eaau8866
DOI: 10.1126/scitranslmed.aau8866

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Killing two birds with one protein

Anthracyclines, a class of common chemotherapy drugs, frequently cause cardiac damage. This cardiotoxicity is associated with activation of p53, a protein that stimulates apoptosis in tumors and in other organs such as the heart, causing nonspecific tissue injury. Saleme et al. found that pyruvate kinase muscle 2 (PKM2) directly interacts with p53. The tetrameric form of PKM2 is preferentially oxidized in the heart, where it suppresses apoptosis. Conversely, the same tetramer enhances the activity of p53 in low oxidation environments such as tumors. The authors identified a compound that stabilizes tetrameric PKM2, protecting cardiomyocytes while facilitating cancer cell killing by anthracyclines.