scholarly journals Escherichia coli Cytotoxic Necrotizing Factor 1 Blocks Cell Cycle G2/M Transition in Uroepithelial Cells

2006 ◽  
Vol 74 (7) ◽  
pp. 3765-3772 ◽  
Author(s):  
Loredana Falzano ◽  
Perla Filippini ◽  
Sara Travaglione ◽  
Alessandro Giamboi Miraglia ◽  
Alessia Fabbri ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Cell Cycle ◽  
Rho Gtpases ◽  
Cell Cycle Progression ◽  
Cyclin B1 ◽  
Eukaryotic Cell ◽  
Cytotoxic Necrotizing Factor ◽  
Cytoskeleton Organization ◽  
Protein Toxin ◽  
Cytotoxic Necrotizing Factor 1

ABSTRACT Evidence is accumulating that a growing number of bacterial toxins act by modulating the eukaryotic cell cycle machinery. In this context, we provide evidence that a protein toxin named cytotoxic necrotizing factor 1 (CNF1) from uropathogenic Escherichia coli is able to block cell cycle G2/M transition in the uroepithelial cell line T24. CNF1 permanently activates the small GTP-binding proteins of the Rho family that, beside controlling the actin cytoskeleton organization, also play a pivotal role in a large number of other cellular processes, including cell cycle regulation. The results reported here show that CNF1 is able to induce the accumulation of cells in the G2/M phase by sequestering cyclin B1 in the cytoplasm and down-regulating its expression. The possible role played by the Rho GTPases in the toxin-induced cell cycle deregulation has been investigated and discussed. The activity of CNF1 on cell cycle progression can offer a novel view of E. coli pathogenicity.

The Escherichia coli protein toxin cytotoxic necrotizing factor 1 induces epithelial mesenchymal transition

2019 ◽  
Vol 22 (2) ◽  
Author(s):  
Alessia Fabbri ◽  
Sara Travaglione ◽  
Francesca Rosadi ◽  
Giulia Ballan ◽  
Zaira Maroccia ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition ◽  
Cytotoxic Necrotizing Factor ◽  
Protein Toxin ◽  
Cytotoxic Necrotizing Factor 1

scholarly journals Cell adhesion is regulated by CDK1 during the cell cycle

2018 ◽  
Vol 217 (9) ◽  
pp. 3203-3218 ◽  
Author(s):  
Matthew C. Jones ◽  
Janet A. Askari ◽  
Jonathan D. Humphries ◽  
Martin J. Humphries
Keyword(s):  
Cell Cycle ◽  
Cell Adhesion ◽  
Actin Cytoskeleton ◽  
Cell Cycle Progression ◽  
Cyclin B1 ◽  
Cycle Progression ◽  
Cytoskeleton Organization ◽  
Actin Cytoskeleton Organization ◽  
Dependent Growth ◽  
Adhesion Complex

In most tissues, anchorage-dependent growth and cell cycle progression are dependent on cells engaging extracellular matrices (ECMs) via integrin–receptor adhesion complexes. In a highly conserved manner, cells disassemble adhesion complexes, round up, and retract from their surroundings before division, suggestive of a primordial link between the cell cycle machinery and the regulation of cell adhesion to the ECM. In this study, we demonstrate that cyclin-dependent kinase 1 (CDK1) mediates this link. CDK1, in complex with cyclin A2, promotes adhesion complex and actin cytoskeleton organization during interphase and mediates a large increase in adhesion complex area as cells transition from G1 into S. Adhesion complex area decreases in G2, and disassembly occurs several hours before mitosis. This loss requires elevated cyclin B1 levels and is caused by inhibitory phosphorylation of CDK1–cyclin complexes. The inactivation of CDK1 is therefore the trigger that initiates remodeling of adhesion complexes and the actin cytoskeleton in preparation for rapid entry into mitosis.

scholarly journals Activation of Rho GTPases by Cytotoxic Necrotizing Factor 1 Induces Macropinocytosis and Scavenging Activity in Epithelial Cells

2001 ◽  
Vol 12 (7) ◽  
pp. 2061-2073 ◽  
Author(s):  
Carla Fiorentini ◽  
Loredana Falzano ◽  
Alessia Fabbri ◽  
Annarita Stringaro ◽  
Mariaantonia Logozzi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Rho Gtpases ◽  
Cell Function ◽  
Apoptotic Cells ◽  
Scavenging Activity ◽  
Cytotoxic Necrotizing Factor ◽  
Protein Toxin ◽  
Mucosal Tissues ◽  
Large Material ◽  
Cytotoxic Necrotizing Factor 1

Macropinocytosis, a ruffling-driven process that allows the capture of large material, is an essential aspect of normal cell function. It can be either constitutive, as in professional phagocytes where it ends with the digestion of captured material, or induced, as in epithelial cells stimulated by growth factors. In this case, the internalized material recycles back to the cell surface. We herein show that activation of Rho GTPases by a bacterial protein toxin, theEscherichia coli cytotoxic necrotizing factor 1 (CNF1), allowed epithelial cells to engulf and digest apoptotic cells in a manner similar to that of professional phagocytes. In particular, we have demonstrated that 1) the activation of all Rho, Rac, and Cdc42 by CNF1 was essential for the capture and internalization of apoptotic cells; and 2) such activation allowed the discharge of macropinosomal content into Rab7 and lysosomal associated membrane protein-1 acidic lysosomal vesicles where the ingested particles underwent degradation. Taken together, these findings indicate that CNF1-induced “switching on” of Rho GTPases may induce in epithelial cells a scavenging activity, comparable to that exerted by professional phagocytes. The activation of such activity in epithelial cells may be relevant, in mucosal tissues, in supporting or integrating the scavenging activity of resident macrophages.

scholarly journals HCF-1 promotes cell cycle progression by regulating the expression of CDC42

2020 ◽  
Vol 11 (10) ◽  
Author(s):  
Pan Xiang ◽  
Fei Li ◽  
Zhihua Ma ◽  
Jiping Yue ◽  
Cailing Lu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromosome Segregation ◽  
Rho Gtpases ◽  
Cell Cycle Progression ◽  
Eukaryotic Cell ◽  
Transcription Start ◽  
Cycle Progression ◽  
Cellular Processes ◽  
Host Cell Factor 1 ◽  
Regulation Mode

Abstract The eukaryotic cell cycle involves a highly orchestrated series of events in which the cellular genome is replicated during a synthesis (S) phase and each of the two resulting copies are segregated properly during mitosis (M). Host cell factor-1 (HCF-1) is a transcriptional co-regulator that is essential for and has been implicated in basic cellular processes, such as transcriptional regulation and cell cycle progression. Although a series of HCF-1 transcriptional targets have been identified, few functional clues have been provided, especially for chromosome segregation. Our results showed that HCF-1 activated CDC42 expression by binding to the −881 to −575 region upstream of the CDC42 transcription start site, and the regulation of CDC42 expression by HCF-1 was correlated with cell cycle progression. The overexpression of a spontaneously cycling and constitutively active CDC42 mutant (CDC42F28L) rescued G1 phase delay and multinucleate defects in mitosis upon the loss of HCF-1. Therefore, these results establish that HCF-1 ensures proper cell cycle progression by regulating the expression of CDC42, which indicates a possible mechanism of cell cycle coordination and the regulation mode of typical Rho GTPases.

scholarly journals Cytotoxic Necrotizing Factor 1 and Hemolysin from Uropathogenic Escherichia coli Elicit Different Host Responses in the Murine Bladder

2012 ◽  
Vol 81 (1) ◽  
pp. 99-109 ◽  
Author(s):  
Tamako A. Garcia ◽  
Christy L. Ventura ◽  
Mark A. Smith ◽  
D. Scott Merrell ◽  
Alison D. O'Brien
Keyword(s):  
Escherichia Coli ◽  
Innate Immunity ◽  
Rho Gtpases ◽  
Negative Impact ◽  
Proinflammatory Response ◽  
Bladder Tissue ◽  
Content Type ◽  
Cytotoxic Necrotizing Factor ◽  
Expression Of Genes ◽  
Cytotoxic Necrotizing Factor 1

Cytotoxic necrotizing factor 1 (CNF1) and hemolysin (HlyA1) are toxins produced by uropathogenicEscherichia coli(UPEC). We previously showed that these toxins contribute to the inflammation and tissue damage seen in a mouse model of ascending urinary tract infection. CNF1 constitutively activates small Rho GTPases by deamidation of a conserved glutamine residue, and HlyA1 forms pores in eukaryotic cell membranes. In this study, we used cDNA microarrays of bladder tissue isolated from mice infected intraurethrally with wild-type CP9, CP9cnf1, or CP9ΔhlyAto further evaluate the role that each toxin plays in the host response to UPEC. Regardless of the strain used, we found that UPEC itself elicited a significant change in host gene expression 24 h after inoculation. The largest numbers of upregulated genes were in the cytokine and chemokine signaling and Toll-like receptor signaling pathways. CNF1 exerted a strong positive influence on expression of genes involved in innate immunity and signal transduction and a negative impact on metabolism- and transport-associated genes. HlyA1 evoked an increase in expression of genes that encode innate immunity factors and a decrease in expression of genes involved in cytoskeletal and metabolic processes. Multiplex cytokine and myeloperoxidase assays corroborated our finding that a strong proinflammatory response was elicited by all strains tested. Bladders challenged intraurethrally with purified CNF1 displayed pathology similar to but significantly less intense than the pathology that we observed in CP9-challenged mice. Our data demonstrate substantial roles for CNF1 and HlyA1 in initiation of a strong proinflammatory response to UPEC in the bladder.

scholarly journals Effects of the Escherichia coli Bacterial Toxin Cytotoxic Necrotizing Factor 1 on Different Human and Animal Cells: A Systematic Review

2021 ◽  
Vol 22 (22) ◽  
pp. 12610
Author(s):  
Francesca Carlini ◽  
Zaira Maroccia ◽  
Carla Fiorentini ◽  
Sara Travaglione ◽  
Alessia Fabbri
Keyword(s):  
Escherichia Coli ◽  
Rho Gtpases ◽  
Cultured Cells ◽  
Bacterial Toxin ◽  
Animal Cells ◽  
Eligibility Criteria ◽  
Cytotoxic Necrotizing Factor ◽  
Small Proteins ◽  
Cytotoxic Necrotizing Factor 1

Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor, the target of which is represented by Rho GTPases, small proteins involved in a huge number of crucial cellular processes. CNF1, due to its ability to modulate the activity of Rho GTPases, represents a widely used tool to unravel the role played by these regulatory proteins in different biological processes. In this review, we summarized the data available in the scientific literature concerning the observed in vitro effects induced by CNF1. An article search was performed on electronic bibliographic resources. Screenings were performed of titles, abstracts, and full-texts according to PRISMA guidelines, whereas eligibility criteria were defined for in vitro studies. We identified a total of 299 records by electronic article search and included 76 original peer-reviewed scientific articles reporting morphological or biochemical modifications induced in vitro by soluble CNF1, either recombinant or from pathogenic Escherichia coli extracts highly purified with chromatographic methods. Most of the described CNF1-induced effects on cultured cells are ascribable to the modulating activity of the toxin on Rho GTPases and the consequent effects on actin cytoskeleton organization. All in all, the present review could be a prospectus about the CNF1-induced effects on cultured cells reported so far.

scholarly journals Cleavage of Escherichia coli Cytotoxic Necrotizing Factor 1 Is Required for Full Biologic Activity

2009 ◽  
Vol 77 (5) ◽  
pp. 1835-1841 ◽  
Author(s):  
Zeynep Knust ◽  
Britta Blumenthal ◽  
Klaus Aktories ◽  
Gudula Schmidt
Keyword(s):  
Escherichia Coli ◽  
Mammalian Cells ◽  
Catalytic Domain ◽  
Small Gtpases ◽  
Gtp Hydrolysis ◽  
Cytotoxic Necrotizing Factor ◽  
Endosomal Membrane ◽  
Protein Toxin ◽  
Late Endosomes ◽  
Cytotoxic Necrotizing Factor 1

ABSTRACT Cytotoxic necrotizing factor 1 (CNF1) is a protein toxin produced by pathogenic Escherichia coli strains. CNF1 constitutively activates small GTPases of the Rho family by deamidation of a glutamine, which is crucial for GTP hydrolysis. The toxin is taken up into mammalian cells by receptor-mediated endocytosis and is delivered from late endosomes into the cytosol. Here, we show that an approximately 55-kDa fragment of CNF1, which contains the catalytic domain and an additional part of the toxin, is present in the cytosol. The processing of this fragment requires an acidic pH and insertion of the toxin into the endosomal membrane. We define the cleavage site region as the region located between amino acids 532 and 544 of CNF1. The data provide insight into the complex mechanism of uptake of bacterial toxins into mammalian cells.

Cyclin specificity: how many wheels do you need on a unicycle?

2001 ◽  
Vol 114 (10) ◽  
pp. 1811-1820 ◽  
Author(s):  
M.E. Miller ◽  
F.R. Cross
Keyword(s):  
Cell Cycle ◽  
Subcellular Localization ◽  
Cell Cycle Progression ◽  
Eukaryotic Cell ◽  
Cyclin Dependent Kinase ◽  
Temporal Expression ◽  
Cycle Progression

Cyclin-dependent kinase (CDK) activity is essential for eukaryotic cell cycle events. Multiple cyclins activate CDKs in all eukaryotes, but it is unclear whether multiple cyclins are really required for cell cycle progression. It has been argued that cyclins may predominantly act as simple enzymatic activators of CDKs; in opposition to this idea, it has been argued that cyclins might target the activated CDK to particular substrates or inhibitors. Such targeting might occur through a combination of factors, including temporal expression, protein associations, and subcellular localization.

scholarly journals Cyclin B1/CDK1-regulated mitochondrial bioenergetics in cell cycle progression and tumor resistance

2019 ◽  
Vol 443 ◽  
pp. 56-66 ◽  
Author(s):  
Bowen Xie ◽  
Shuangyan Wang ◽  
Nian Jiang ◽  
Jian Jian Li
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Cyclin B1 ◽  
Mitochondrial Bioenergetics ◽  
Tumor Resistance ◽  
Cycle Progression
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