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PML is a ROS sensor activating p53 upon oxidative stress

ABSTRACT: PML nuclear bodies (NBs) recruit partner proteins -including p53 and its regulators- controlling their abundance or function. Investigating arsenic sensitivity of acute promyelocytic leukemia, we proposed that PML oxidation promotes NB-biogenesis. Yet, physiological links between PML and oxidative stress response in vivo remain unexplored. Here we identify PML as a reactive oxygen species (ROS) sensor. Pml-/- cells accumulate ROS, while PML expression decreases ROS levels. Unexpectedly, Pml-/- embryos survive acute glutathione depletion. Moreover, Pml-/- animals are resistant to acetaminophen hepatotoxicity or fasting-induced steatosis. Molecularly, Pml-/- animals fail to properly activate oxidative stress-responsive p53 targets, while NRF2 response is accelerated. Finally, in an oxidative stress-prone background, Pml-/- animals display a longevity phenotype, likely reflecting decreased basal p53 activation. Thus, similar to p53, PML exerts basal anti-oxidant 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 PML role in senescence or stem cell biology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE103642 | GEO | 2017/09/22

SECONDARY ACCESSION(S): PRJNA403838

REPOSITORIES: GEO

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Unbiased in vivo exploration of nuclear bodies-enhanced sumoylation reveals that PML orchestrates embryonic stem cell fate (II)

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Homo sapiens

Project description:PML is a ROS sensor activating p53 upon oxidative stress

| PRJNA403838 | ENA

PML is a ROS sensor activating p53 upon oxidative stress

Project description:PML is a ROS sensor activating p53 upon oxidative stress

| PRJNA392300 | ENA

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