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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

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2022-09-14 | PXD028865 | Pride

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

2023-03-06 | PXD032240 | Pride

PML Nuclear Bodies are stress-responsive sumoylation/degradation compartments regulating KAP1 silencing function in embryonic stem cells

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2022-09-14 | PXD019609 | Pride

Gene expression profiling of Pml wt and Pml KO mice liver with acetaminophen (apap) overdose (300mg/kg) i.p.

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Gene expression profiling of Pml wt and Pml KO mice liver after fasted 6h

Project description:The Pml gene is essential to the formation of PML nuclear bodies, domains which have been associated with various functions such as apoptosis/senescence, DNA repair and cell proliferation( Lallemand-Breitenbach 2010). PML-NBs formation is regulated by cellular stress including oxidative stress(Jeanne 2010, de The 2012). To investigate the role of PML in ROS response in vivo, we analyse the expression difference betweem Pml wt and Pml KO under fasted condition, which easily up-regulate ROS in BALB/cByJ background

2017-09-22 | GSE100615 | GEO

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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Proximity labelling with TurboID shows that client proteins of PML NBs differ in three cell contexts

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2023-01-10 | PXD037432 | Pride

Identifying chromatin associations with promyelocytic leukemia nuclear bodies using immunoTRAP

Project description:Studies using fluorescence in situ hybridization (FISH) have attempted to determine whether specific gene loci associate with promyelocytic leukemia nuclear bodies (PML NBs). Two drawbacks accompany this approach; the lack of spatial resolution inherent with the technique, and the a priori basis for selecting which genes to probe. To overcome these limitations, we developed a technique, which we call immunoTRAP, which purifies the DNA contacting PML NBs at molecular dimensions. When we combined the immunoTRAP technique with immunoFISH and microarray analysis, not only did we verify a TP53-PML NB association, but were able also to identify novel locus associations such as PML, ABCA7, and TFF1. In addition, we observed that these associations are cell type specific, and induction of significantly higher levels of PML gene expression, as well as other physiological changes brought about by interferon treatment, can lead to a physical association of the PML gene with PML NBs in normal human fibroblasts. Thus, immunoTRAP is a technique capable of identifying the chromatin associations around nuclear subcompartments and is amenable for further downstream applications such as microarray analysis or deep sequencing. Identification of binding (Cy5) to PML vs. to non-specific binding in Jurkat cells (n=5)

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