The tumor suppressor Pml regulates cell fate in the developing neocortex

Regad, Tarik; Bellodi, Cristian; Nicotera, Pierluigi; Salomoni, Paolo

doi:10.1038/nn.2251

Cited by 109 publications

(151 citation statements)

References 56 publications

Supporting

Mentioning

142

Contrasting

Unclassified

Order By: Relevance

“…Because, according to previous reports (Regad et al 2009), loss of PML appears to affect neurogenesis, it was reasonable to hypothesize that PML might regulate plasticity and behavior in normal brain function. Indeed, our research suggest that, while PML knockout mice seem normal regarding control parameters (motoric and sensory demands), when subjected to behavioral tests, they present differences respect to the control group regarding learning/memory as well as emotional/motivational assessments.…”

Section: Discussionmentioning

confidence: 89%

“…However, the key players involved in these processes remain unknown. Recent work has pointed to a role of PML in brain development (Regad et al 2009) by demonstrating that PML expression in neuronal progenitor cells (NPCs) of the neocortex appears to limit NPC proliferation favoring neuronal differentiation. Thus, because PML expression is associated with highly proliferative germinal zones in the developing brain, it is reasonable to hypothesize that PML might be involved in controlling neuronal stem cell function and pathological conditions associated with neurogenesis.…”

mentioning

confidence: 99%

“…Thus, because PML has been associated with highly proliferative germinal zones in the brain and neurogenesis appears to be important for learning and memory, it is reasonable to hypothesize that PML could play a role in cognition and plasticity. Whereas the physiological relevance of intracerebral PML is starting to emerge (Regad et al 2009), very little is known regarding its function in the brain. Herein, to evaluate a possible role of this protein in the CNS, we first determined whether PML is indeed present and important in the brain.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Impaired cognitive function and reduced anxiety‐related behavior in a promyelocytic leukemia (PML) tumor suppressor protein‐deficient mouse

Butler

Martínez

Tejada‐Simon

2013

Genes Brain and Behavior

View full text Add to dashboard Cite

The promyelocytic leukemia (PML) protein is a tumor suppressor factor mostly known by its involvement in acute promyelocytic leukemia (APL). Interestingly, recent studies have provided evidence that, in the central nervous system, PML is involved in neurogenesis. However, prospective studies of PML in brain are lacking. To further understand the role of PML in the mammalian brain, we studied plasticity and behavioral changes in PML knockout mice. If PML is involved in neurogenesis, and neurogenesis is an important process for proper brain development as well as learning and memory functions, we hypothesized that PML might have a role in plasticity and cognition. Behavioral studies demonstrated that PML knockout mice present abnormalities in conditioned learning and spatial memory, as determined by fear conditioning and Morris water maze tasks. Experiments to determine normal exploratory behavior interestingly revealed that PML knockout mice present reduced anxiety-related responses as compared to control animals. This was confirmed when PML knockout mice spent more time in the open arms of an elevated plus-maze, which is an indication of decreased anxiety. Additionally, impairments in hippocampus-dependent learning were mirrored by altered long-term plasticity at Schaffer collateral-CA1 synapses. We now provide the first evidence for an important role of PML in the brain, indicating that PML might have a role in synaptic plasticity and associated behavioral processes.

show abstract

Section: Discussionmentioning

confidence: 89%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Impaired cognitive function and reduced anxiety‐related behavior in a promyelocytic leukemia (PML) tumor suppressor protein‐deficient mouse

Butler

Martínez

Tejada‐Simon

2013

Genes Brain and Behavior

View full text Add to dashboard Cite

show abstract

“…40). Often in their sumoylated forms, some partners have been implicated in IFN effects on senescence (DAXX, p53, SP100) or antiviral defence (SP100) [41][42][43][44][45][46] . These unexpected findings therefore point to the existence of a highly integrated regulatory loop wherein the substrates, their modifiers (SUMOs) and the catalyser (PML NBs) are all dramatically upregulated during IFN response, promoting the rapid formation of the active, SUMO-conjugated form.…”

Section: Discussionmentioning

confidence: 99%

Interferon controls SUMO availability via the Lin28 and let-7 axis to impede virus replication

Şahin¹,

Ferhi²,

Carnec³

et al. 2014

Nat Commun

View full text Add to dashboard Cite

Small ubiquitin-related modifier (SUMO) protein conjugation onto target proteins regulates multiple cellular functions, including defence against pathogens, stemness and senescence. SUMO1 peptides are limiting in quantity and are thus mainly conjugated to high-affinity targets. Conjugation of SUMO2/3 paralogues is primarily stress inducible and may initiate target degradation. Here we demonstrate that the expression of SUMO1/2/3 is dramatically enhanced by interferons through an miRNA-based mechanism involving the Lin28/let-7 axis, a master regulator of stemness. Normal haematopoietic progenitors indeed display much higher SUMO contents than their differentiated progeny. Critically, SUMOs contribute to the antiviral effects of interferons against HSV1 or HIV. Promyelocytic leukemia (PML) nuclear bodies are interferon-induced domains, which facilitate sumoylation of a subset of targets. Our findings thus identify an integrated interferon-responsive PML/SUMO pathway that impedes viral replication by enhancing SUMO conjugation and possibly also modifying the repertoire of targets. Interferon-enhanced post-translational modifications may be essential for senescence or stem cell self-renewal, and initiate SUMO-dependent proteolysis.

show abstract

“…PML protein is highly enriched in germinal areas including ventricular zone of the neocortex suggesting that PML is associated with the immature state of neural progenitors. 18) PML is also highly enriched in immature hemopoietic progenitors and leukemia-initiating cells. 9) Our results indicated that PML might be highly expressed in the tumor-initiating cells of medulloblastoma.…”

Section: Discussionmentioning

confidence: 99%

Molecular Targeting Therapy Against Promyelocytic Leukemia Protein Using Arsenic Acids in Experimental Intracranial Medulloblastoma

Yokota

Gao

et al. 2012

Neurol. Med. Chir.(Tokyo)

View full text Add to dashboard Cite

The tumor suppressor Pml regulates cell fate in the developing neocortex

Cited by 109 publications

References 56 publications

Impaired cognitive function and reduced anxiety‐related behavior in a promyelocytic leukemia (PML) tumor suppressor protein‐deficient mouse

Impaired cognitive function and reduced anxiety‐related behavior in a promyelocytic leukemia (PML) tumor suppressor protein‐deficient mouse

Interferon controls SUMO availability via the Lin28 and let-7 axis to impede virus replication

Molecular Targeting Therapy Against Promyelocytic Leukemia Protein Using Arsenic Acids in Experimental Intracranial Medulloblastoma

Contact Info

Product

Resources

About