PML is a ROS sensor activating p53 upon oxidative stress
Promyelocytic leukemia (PML) nuclear bodies (NBs) recruit partner proteins, including p53 and its regulators, thereby controlling their abundance or function. Investigating arsenic sensitivity of acute promyelocytic leukemia, we proposed that PML oxidation promotes NB biogenesis. However, physiologi...
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Published in | The Journal of experimental medicine Vol. 214; no. 11; pp. 3197 - 3206 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Rockefeller University Press
06.11.2017
The Rockefeller University Press |
Subjects | |
Online Access | Get full text |
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Summary: | Promyelocytic leukemia (PML) nuclear bodies (NBs) recruit partner proteins, including p53 and its regulators, thereby controlling their abundance or function. Investigating arsenic sensitivity of acute promyelocytic leukemia, we proposed that PML oxidation promotes NB biogenesis. However, physiological links between PML and oxidative stress response in vivo remain unexplored. Here, we identify PML as a reactive oxygen species (ROS) sensor.
cells accumulate ROS, whereas PML expression decreases ROS levels. Unexpectedly,
embryos survive acute glutathione depletion. Moreover,
animals are resistant to acetaminophen hepatotoxicity or fasting-induced steatosis. Molecularly,
animals fail to properly activate oxidative stress-responsive p53 targets, whereas the NRF2 response is amplified and accelerated. Finally, in an oxidative stress-prone background,
animals display a longevity phenotype, likely reflecting decreased basal p53 activation. Thus, similar to p53, PML exerts basal antioxidant properties but also drives oxidative stress-induced changes in cell survival/proliferation or metabolism in vivo. Through NB biogenesis, PML therefore couples ROS sensing to p53 responses, shedding a new light on the role of PML in senescence or stem cell biology. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 PMCID: PMC5679165 V. Lallemand-Breitenbach and H. de Thé contributed equally to this paper. |
ISSN: | 0022-1007 1540-9538 |
DOI: | 10.1084/jem.20160301 |