p73 Regulates Primary Cortical Neuron Metabolism: a Global Metabolic Profile

Agostini, Massimiliano; Niklison-Chirou, Maria Victoria; Annicchiarico-Petruzzelli, Margherita; Grelli, Sandro; Daniele, Nicola Di; Pestlikis, Ilias; Knight, Richard; Melino, Gerry; Rufini, Alessandro

doi:10.1007/s12035-017-0517-3

Cited by 9 publications

(3 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Specifically, loss of TAp73 seems to increase glycolysis, whereas loss of DeltaNp73 reduces glucose metabolism (Agostini et al. ). TAp73 also regulates the synthesis of the enzyme glutaminase isoform 2 (GLS2) that converts glutamine into glutamate.…”

Section: Discussionmentioning

confidence: 99%

Cajal‐Retzius neurons are required for the development of the human hippocampal fissure

et al. 2019

View full text Add to dashboard Cite

Cajal-Retzius neurons (CRN) are the main source of Reelin in the marginal zone of the developing neocortex and hippocampus (HC). They also express the transcription factor p73 and are complemented by laterappearing GABAergic Reelin + interneurons. The human dorsal HC forms at gestational week 10 (GW10), when it develops a rudimentary Ammonic plate and incipient dentate migration, although the dorsal hippocampal fissure (HF) remains shallow and contains few CRN. The dorsal HC transforms into the indusium griseum (IG), concurrently with the rostro-caudal appearance of the corpus callosum, by GW14-17. Dorsal and ventral HC merge at the site of the former caudal hem, which is located at the level of the future atrium of the lateral ventricle and closely connected with the choroid plexus. The ventral HC forms at GW11 in the temporal lobe. The ventral HF is wide open at GW14-16 and densely populated by large numbers of CRNs. These are in intimate contact with the meninges and meningeal blood vessels, suggesting signalling through diverse pathways. At GW17, the fissure deepens and begins to fuse, although it is still marked by p73/Reelin + CRNs. The p73KO mouse illustrates the importance of p73 in CRN for HF formation. In the mutant, Tbr1/Reelin + CRNs are born in the hem but do not leave it and subsequently disappear, so that the mutant cortex and HC lack CRN from the onset of corticogenesis. The HF is absent, which leads to profound architectonic alterations of the HC. To determine which p73 isoform is important for HF formation, isoform-specific TAp73-and DeltaNp73deficient embryonic and early postnatal mice were examined. In both mutants, the number of CRNs was reduced, but each of their phenotypes was much milder than in the global p73KO mutant missing both isoforms. In the TAp73KO mice, the HF of the dorsal HC failed to form, but was present in the ventral HC. In the DeltaNp73KO mice, the HC had a mild patterning defect along with a shorter HF. Complex interactions between both isoforms in CRNs may contribute to their crucial activity in the developing brain.Sections were deparaffinized, hydrated, and boiled in 10 mM citrate buffer (pH 6) for 20 min for antigen retrieval, rinsed in Trisbuffered saline (TBS, pH 7.6, 0.05 M), and incubated in the primary antibodies overnight in a humid chamber. After rinsing, they were incubated in the corresponding biotinylated secondary antibodies (rabbit anti-mouse IgG or goat anti-rabbit IgG; Dako, Glostrup, Denmark), diluted at 1 : 200 in TBS, followed by incubation with avidin-biotin complex (ABC, DAKO) in TBS. Bound peroxidase was

show abstract

Section: Discussionmentioning

confidence: 99%

Cajal‐Retzius neurons are required for the development of the human hippocampal fissure

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Accordingly, pramlintide, a synthetic analogue of amylin, causes rapid tumor regression of p53-deficient thymic lymphomas in mice [253]. Furthermore, high-throughput metabolic analysis of ∆Np73 −/− mice neurons showed slightly reduced glycolysis and reduced amounts of membrane phospholipids, long-chain fatty acids, sphingolipids [254], N-acetylaspartylglutamate, and neurotransmitter glycine, suggesting a delay in neuronal differentiation [251]. Interestingly, inhibition of polyamine catabolism decreases the ∆Np73/TAp73 ratio in favor of TAp73 and restores sensitivity of the monocytic leukemic cells THP-1 to doxorubicin [255].…”

Section: Biological Activity and Functions Of The P73 Isoformsmentioning

confidence: 99%

p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies

Horvat

Tadijan

Vlašić

et al. 2021

Cancers

View full text Add to dashboard Cite

The p53 tumor suppressor protein is crucial for cell growth control and the maintenance of genomic stability. Later discovered, p63 and p73 share structural and functional similarity with p53. To understand the p53 pathways more profoundly, all family members should be considered. Each family member possesses two promoters and alternative translation initiation sites, and they undergo alternative splicing, generating multiple isoforms. The resulting isoforms have important roles in carcinogenesis, while their expression is dysregulated in several human tumors including colorectal carcinoma, which makes them potential targets in cancer treatment. Their activities arise, at least in part, from the ability to form tetramers that bind to specific DNA sequences and activate the transcription of target genes. In this review, we summarize the current understanding of the biological activities and regulation of the p53/p73 isoforms, highlighting their role in colorectal tumorigenesis. The analysis of the expression patterns of the p53/p73 isoforms in human cancers provides an important step in the improvement of cancer therapy. Furthermore, the interactions among the p53 family members which could modulate normal functions of the canonical p53 in tumor tissue are described. Lastly, we emphasize the importance of clinical studies to assess the significance of combining the deregulation of different members of the p53 family to define the outcome of the disease.

show abstract

“…Moreover, p73 is essential for maintaining the neurogenic pool in SVZ and SGZ by promoting self-renewal and proliferation and inhibiting premature senescence of NSCs and/or NPCs [ 148 , 149 , 150 ]. Mechanistically, TAp73 either directly or indirectly regulates the expression of genes involved in metabolism [ 151 , 152 , 153 ] and NSCs maintenance including, Sox2, Sox3, TRIM32 and Notch signalling pathway. Similarly, TAp73 regulates NSCs maintenance in the olfactory bulb by transcriptionally regulating the expression of Hey-2 [ 154 ].…”

Section: Transcriptional Regulation Of Adult Neurogenesismentioning

confidence: 99%

Regulation of Adult Neurogenesis in Mammalian Brain

Niklison-Chirou

Agostini

Amelio

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Adult neurogenesis is a multistage process by which neurons are generated and integrated into existing neuronal circuits. In the adult brain, neurogenesis is mainly localized in two specialized niches, the subgranular zone (SGZ) of the dentate gyrus and the subventricular zone (SVZ) adjacent to the lateral ventricles. Neurogenesis plays a fundamental role in postnatal brain, where it is required for neuronal plasticity. Moreover, perturbation of adult neurogenesis contributes to several human diseases, including cognitive impairment and neurodegenerative diseases. The interplay between extrinsic and intrinsic factors is fundamental in regulating neurogenesis. Over the past decades, several studies on intrinsic pathways, including transcription factors, have highlighted their fundamental role in regulating every stage of neurogenesis. However, it is likely that transcriptional regulation is part of a more sophisticated regulatory network, which includes epigenetic modifications, non-coding RNAs and metabolic pathways. Here, we review recent findings that advance our knowledge in epigenetic, transcriptional and metabolic regulation of adult neurogenesis in the SGZ of the hippocampus, with a special attention to the p53-family of transcription factors.

show abstract

p73 Regulates Primary Cortical Neuron Metabolism: a Global Metabolic Profile

Cited by 9 publications

References 71 publications

Cajal‐Retzius neurons are required for the development of the human hippocampal fissure

Cajal‐Retzius neurons are required for the development of the human hippocampal fissure

p53/p73 Protein Network in Colorectal Cancer and Other Human Malignancies

Regulation of Adult Neurogenesis in Mammalian Brain

Contact Info

Product

Resources

About