Phosphoinositide 3-kinase signalling in the nucleolus

Morovicz, Andrea Papdiné; Gavgani, Fatemeh Mazloumi; Jacobsen, Rhian Gaenor; Slinning, Malene Skuseth; Turcu, Diana Cornelia; Lewis, Aurélia E.

doi:10.1016/j.jbior.2021.100843

Cited by 11 publications

(3 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phosphorylation of these proteins could alter their interaction with rDNA, and lead to reduced rRNA transcription. Similar phosphorylation-mediated regulation of Pol I transcription has been reported, involving key signaling cascades, such as PI3K/AKT/mTOR and the MAPK/ERK pathways ( Grummt, 2003 ; Morovicz et al, 2021 ). Upon different external stimuli, these kinases are responsible for phosphorylating members of the Pol I holo-complex, such as SL1 components, TTF1 or UBF, thereby leading to stimulation/inhibition of rRNA transcription ( Stefanovsky et al, 2001 ; Zhao et al, 2003 ; Mayer et al, 2004 ; Nguyen and Mitchell, 2013 ).…”

Section: Treacle Is a Central Regulator Of Nucleolar Stress Responsessupporting

confidence: 71%

Treacle Sticks the Nucleolar Responses to DNA Damage Together

Gál

Nieto

Boukoura

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

The importance of chromatin environment for DNA repair has gained increasing recognition in recent years. The nucleolus is the largest sub-compartment within the nucleus: it has distinct biophysical properties, selective protein retention, and houses the specialized ribosomal RNA genes (collectively referred to as rDNA) with a unique chromatin composition. These genes have high transcriptional activity and a repetitive nature, making them susceptible to DNA damage and resulting in the highest frequency of rearrangements across the genome. A distinct DNA damage response (DDR) secures the fidelity of this genomic region, the so-called nucleolar DDR (n-DDR). The composition of the n-DDR reflects the characteristics of nucleolar chromatin with the nucleolar protein Treacle (also referred to as TCOF1) as a central coordinator retaining several well-characterized DDR proteins in the nucleolus. In this review, we bring together data on the structure of Treacle, its known functions in ribosome biogenesis, and its involvement in multiple branches of the n-DDR to discuss their interconnection. Furthermore, we discuss how the functions of Treacle in ribosome biogenesis and in the n-DDR may contribute to Treacher Collins Syndrome, a disease caused by mutations in Treacle. Finally, we outline outstanding questions that need to be addressed for a more comprehensive understanding of Treacle, the n-DDR, and the coordination of ribosome biogenesis and DNA repair.

show abstract

Section: Treacle Is a Central Regulator Of Nucleolar Stress Responsessupporting

confidence: 71%

Treacle Sticks the Nucleolar Responses to DNA Damage Together

Gál

Nieto

Boukoura

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…It is well known that the phosphatidylinositol-3-kinase, a conserved family of signal transduction enzymes, is implicated in the regulation of cell growth, cycle entry, migration, and survival. [62] Protein kinase B is activated via a PI3K pathway in which PI3K-mediated production of phosphatidylinositol-3,4,5-trisphosphate leads to the recruitment of Akt to the cell membrane and then initiates Akt phosphorylation by phosphoinositide-dependent kinase 1. [63] It was shown that the induction of Heme oxygenase-1 promoted by activation of PI3K/Akt pathway, can play an antiapoptotic and antiinflammatory role in the oxidative damage response to septic lung injury.…”

Section: Discussionmentioning

confidence: 99%

The potential mechanism of the Ruhao Dashi formula in treating acute pneumonia via network pharmacology and molecular docking

Zhou

Chao

et al. 2023

Medicine

View full text Add to dashboard Cite

Background: Acute pneumonia (AP) has a high seasonal prevalence every year, which seriously threatens the lives and health of patients. Six traditional Chinese medicines in Ruhao Dashi formula (RDF) have excellent antiinflammatory, antibacterial, and antiviral effects. RDF is commonly used in the clinical treatment of AP. However, the mechanism and target of RDF are unclear. Therefore, this study aimed to use network pharmacology and molecular docking to evaluate the target and mechanism of RDF in the treatment of AP. Methods: The Herbs and Disease Gene databases were searched to identify common targets of AP and RDF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and Protein-Protein Interaction (PPI) network analyses were performed to identify the potential molecular mechanisms behind RDF. Molecular docking was performed to compare the binding activities of the active molecules with that of the target protein. Results: The “drug-component-common target” network contained 64 active compounds and 134 targets. GO and KEGG analyses indicated that RDF could act by regulating cell death, cell proliferation, apoptosis, and hypoxic response. The PPI network and “pathway-target” network identified 31 core targets. Molecular docking revealed that the 14 active ingredients of RDF bind vigorously to the core targets. Conclusion: Through network pharmacology and molecular docking, we found that RDF contains 14 active components and 31 core AP targets. These targets were linked to the development of an antiinflammatory response and could be used to develop new drugs to treat AP.

show abstract

“…Recent investigations have revealed a close association between ribosomes and tumorigenesis, highlighting their pivotal role in cancer progression [23][24] . Ribosome biogenesis is intricately linked with the PI3K pathway, which governs various crucial regulatory processes 25 .…”

Section: Discussionmentioning

confidence: 99%

SYNGR2 plays a tumor-promoting role in lung adenocarcinoma through PI3K-AKT signaling pathway

Liu,

Luan,

Han

et al. 2023

Preprint

View full text Add to dashboard Cite

Objectives To analyze the expression level of SYNGR2 in lung adenocarcinoma, explored its prognostic and diagnostic value, and preliminarily discussed its mechanism of action. Methods The diagnostic value was assessed by generating the ROC curve using SYNGR2 expression data. COX regression and correlation analysis were conducted to establish its association with clinical features. Additionally, immunohistochemical staining was performed on samples from 20 patients with lung adenocarcinoma (LUAD) to validate the observed differences in expression levels. Furthermore, silencing of SYNGR2 in LUAD cells demonstrated inhibition of proliferation, invasion, migration, and colony formation abilities. Moreover, GO and KEGG analyses along with PPI analysis were employed to preliminarily investigate the underlying mechanism of SYNGR2 in lung adenocarcinoma. Results The results demonstrated an upregulation of SYNGR2 which was associated with shorter overall survival (OS) and progression-free survival (PFS). Furthermore, the receiver operating characteristic (ROC) curve analysis revealed a robust diagnostic value for SYNGR2. Additionally, the SYNGR2 gene exhibited a strong association with the PI3K-AKT signaling pathway. Conclusions SYNGR2 plays a tumor-promoting role in lung adenocarcinoma and may act through PI3K-AKT signaling pathway.

show abstract

Phosphoinositide 3-kinase signalling in the nucleolus

Cited by 11 publications

References 118 publications

Treacle Sticks the Nucleolar Responses to DNA Damage Together

Treacle Sticks the Nucleolar Responses to DNA Damage Together

The potential mechanism of the Ruhao Dashi formula in treating acute pneumonia via network pharmacology and molecular docking

SYNGR2 plays a tumor-promoting role in lung adenocarcinoma through PI3K-AKT signaling pathway

Contact Info

Product

Resources

About