Expression of Nucleolin Affects Microtubule Dynamics

Gaume, Xavier; Place, Christophe; Delage, Hélène; Mongélard, Fabien; Monier, Karine; Bouvet, Philippe

doi:10.1371/journal.pone.0157534

Cited by 5 publications

(4 citation statements)

References 42 publications

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“…Interestingly, each of these reports also found a significant number of nucleolar and ribosomal proteins associated with the mitotic spindle, suggesting a link between the nucleolus, RNA and MT dynamics. Several of these factors have been further shown to regulate MT dynamics, including nucleolin, NPM1 and RPS3 ( 37 , 55 , 56 ). Thus, we hypothesized that FKBP25 could play a similar role in the regulation of MT dynamics.…”

Section: Resultsmentioning

confidence: 99%

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The prolyl isomerase FKBP25 regulates microtubule polymerization impacting cell cycle progression and genomic stability

Dilworth

Gudavicius

et al. 2018

Nucleic Acids Research

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FK506 binding proteins (FKBPs) catalyze the interconversion of cis-trans proline conformers in proteins. Importantly, FK506 drugs have anti-cancer and neuroprotective properties, but the effectors and mechanisms underpinning these properties are not well understood because the cellular function(s) of most FKBP proteins are unclear. FKBP25 is a nuclear prolyl isomerase that interacts directly with nucleic acids and is associated with several DNA/RNA binding proteins. Here, we show the catalytic FKBP domain binds microtubules (MTs) directly to promote their polymerization and stabilize the MT network. Furthermore, FKBP25 associates with the mitotic spindle and regulates entry into mitosis. This interaction is important for mitotic spindle dynamics, as we observe increased chromosome instability in FKBP25 knockdown cells. Finally, we provide evidence that FKBP25 association with chromatin is cell-cycle regulated by Protein Kinase C phosphorylation. This disrupts FKBP25–DNA contacts during mitosis while maintaining its interaction with the spindle apparatus. Collectively, these data support a model where FKBP25 association with chromatin and MTs is carefully choreographed to ensure faithful genome duplication. Additionally, they highlight that FKBP25 is a MT-associated FK506 receptor and potential therapeutic target in MT-associated diseases.

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Section: Resultsmentioning

confidence: 99%

“…Collectively, these observations establish FKBP25 as a bridge between RNA and the cytoskeleton that should be further investigated. The precedent for such a connection is already established from reports of ribosomal proteins, NPM and NCL associating with MTs ( 37 , 55 , 56 ). Notably, these are also FKBP25 interactors ( 31 , 50 ).…”

Section: Discussionmentioning

confidence: 98%

The prolyl isomerase FKBP25 regulates microtubule polymerization impacting cell cycle progression and genomic stability

Dilworth

Gudavicius

et al. 2018

Nucleic Acids Research

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“…In addition, an accumulation of immature centrosomal structures is observed which is accompanied with multipolar centrosomal structures. Recent work also described a function of NCL in microtubule anchorage at centrosome and in microtubules dynamics 28 , 29 .…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, cell shape is drastically affected when NCL expression is reduced 27 – 29 . Many studies have shown that the expression of NCL is required for cell migration or adhesion 34 – 37 .…”

Section: Resultsmentioning

confidence: 99%

Integrated analysis of mRNA and miRNA expression in HeLa cells expressing low levels of Nucleolin

Kumar¹,

Gomez

Chalabi-Dchar

et al. 2017

Sci Rep

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Nucleolin is an essential protein that plays important roles in the regulation of cell cycle and cell proliferation. Its expression is up regulated in many cancer cells but its molecular functions are not well characterized. Nucleolin is present in the nucleus where it regulates gene expression at the transcriptional and post-transcriptional levels. Using HeLa cells depleted in nucleolin we performed an mRNA and miRNA transcriptomics analysis to identify biological pathways involving nucleolin. Bioinformatic analysis strongly points to a role of nucleolin in lipid metabolism, and in many signaling pathways. Down regulation of nucleolin is associated with lower level of cholesterol while the amount of fatty acids is increased. This could be explained by the decreased and mis-localized expression of the transcription factor SREBP1 and the down-regulation of enzymes involved in the beta-oxidation and degradation of fatty acids. Functional classification of the miRNA-mRNA target genes revealed that deregulated miRNAs target genes involved in apoptosis, proliferation and signaling pathways. Several of these deregulated miRNAs have been shown to control lipid metabolism. This integrated transcriptomic analysis uncovers new unexpected roles for nucleolin in metabolic regulation and signaling pathways paving the way to better understand the global function of nucleolin within the cell.

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Nucleolin: a cell portal for viruses, bacteria, and toxins

Tonello

Massimino

Peggion

2022

Cell. Mol. Life Sci.

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The main localization of nucleolin is the nucleolus, but this protein is present in multiple subcellular sites, and it is unconventionally secreted. On the cell surface, nucleolin acts as a receptor for various viruses, some bacteria, and some toxins. Aim of this review is to discuss the characteristics that make nucleolin able to act as receptor or co-receptor of so many and different pathogens. The important features that emerge are its multivalence, and its role as a bridge between the cell surface and the nucleus. Multiple domains, short linear motifs and post-translational modifications confer and modulate nucleolin ability to interact with nucleic acids, with proteins, but also with carbohydrates and lipids. This modular multivalence allows nucleolin to participate in different types of biomolecular condensates and to move to various subcellular locations, where it can act as a kind of molecular glue. It moves from the nucleus to the cell surface and can accompany particles in the reverse direction, from the cell surface into the nucleus, which is the destination of several pathogens to manipulate the cell in their favour.

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Expression of Nucleolin Affects Microtubule Dynamics

Cited by 5 publications

References 42 publications

The prolyl isomerase FKBP25 regulates microtubule polymerization impacting cell cycle progression and genomic stability

The prolyl isomerase FKBP25 regulates microtubule polymerization impacting cell cycle progression and genomic stability

Integrated analysis of mRNA and miRNA expression in HeLa cells expressing low levels of Nucleolin

Nucleolin: a cell portal for viruses, bacteria, and toxins

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