scholarly journals A catabolic block does not sufficiently explain how 2-deoxy-d-glucose inhibits cell growth

2008 ◽  
Vol 105 (46) ◽  
pp. 17807-17811 ◽  
Author(s):  
Markus Ralser ◽  
Mirjam M. Wamelink ◽  
Eduard A. Struys ◽  
Christian Joppich ◽  
Sylvia Krobitsch ◽  
...  
Keyword(s):  
Cell Growth ◽  
Ribosome Biogenesis ◽  
Biological Properties ◽  
Pentose Phosphate ◽  
C Elegans ◽  
Metabolic Block ◽  
A Genome ◽  
Primary Fibroblasts ◽  
Concentration Changes ◽  
Cellular Tolerance

The glucose analogue 2-deoxy-d-glucose (2-DG) restrains growth of normal and malignant cells, prolongs the lifespan of C. elegans, and is widely used as a glycolytic inhibitor to study metabolic activity with regard to cancer, neurodegeneration, calorie restriction, and aging. Here, we report that separating glycolysis and the pentose phosphate pathway highly increases cellular tolerance to 2-DG. This finding indicates that 2-DG does not block cell growth solely by preventing glucose catabolism. In addition, 2-DG provoked similar concentration changes of sugar-phosphate intermediates in wild-type and 2-DG-resistant yeast strains and in human primary fibroblasts. Finally, a genome-wide analysis revealed 19 2-DG-resistant yeast knockouts of genes implicated in carbohydrate metabolism and mitochondrial homeostasis, as well as ribosome biogenesis, mRNA decay, transcriptional regulation, and cell cycle. Thus, processes beyond the metabolic block are essential for the biological properties of 2-DG.

scholarly journals Electrospun Nanofibrous Membranes for Tissue Engineering and Cell Growth

2021 ◽  
Vol 11 (15) ◽  
pp. 6929
Author(s):  
Ewin Tanzli ◽  
Andrea Ehrmann
Keyword(s):  
Tissue Engineering ◽  
Cell Growth ◽  
Polymer Blends ◽  
Mammalian Cells ◽  
Biological Properties ◽  
Specific Substrate ◽  
Electrospun Nanofiber ◽  
Materials Used ◽  
Nanofiber Mats ◽  
Surface Morphologies

In biotechnology, the field of cell cultivation is highly relevant. Cultivated cells can be used, for example, for the development of biopharmaceuticals and in tissue engineering. Commonly, mammalian cells are grown in bioreactors, T-flasks, well plates, etc., without a specific substrate. Nanofibrous mats, however, have been reported to promote cell growth, adhesion, and proliferation. Here, we give an overview of the different attempts at cultivating mammalian cells on electrospun nanofiber mats for biotechnological and biomedical purposes. Starting with a brief overview of the different electrospinning methods, resulting in random or defined fiber orientations in the nanofiber mats, we describe the typical materials used in cell growth applications in biotechnology and tissue engineering. The influence of using different surface morphologies and polymers or polymer blends on the possible application of such nanofiber mats for tissue engineering and other biotechnological applications is discussed. Polymer blends, in particular, can often be used to reach the required combination of mechanical and biological properties, making such nanofiber mats highly suitable for tissue engineering and other biotechnological or biomedical cell growth applications.

JHDM1B expression regulates ribosome biogenesis and cancer cell growth in a p53 dependent manner

2014 ◽  
Vol 136 (5) ◽  
pp. E272-E281 ◽  
Author(s):  
Marianna Penzo ◽  
Lucia Casoli ◽  
Daniela Pollutri ◽  
Laura Sicuro ◽  
Claudio Ceccarelli ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cancer Cell ◽  
Ribosome Biogenesis ◽  
Dependent Manner ◽  
Cancer Cell Growth

scholarly journals Tropomyosin inhibits ADF/cofilin-dependent actin filament dynamics

2002 ◽  
Vol 156 (6) ◽  
pp. 1065-1076 ◽  
Author(s):  
Shoichiro Ono ◽  
Kanako Ono
Keyword(s):  
Actin Filament ◽  
Actin Filaments ◽  
Actin Polymerization ◽  
Biological Properties ◽  
Actin Dynamics ◽  
Background Suppression ◽  
Thin Filaments ◽  
Actin Organization ◽  
C Elegans ◽  
Filament Dynamics

Tropomyosin binds to actin filaments and is implicated in stabilization of actin cytoskeleton. We examined biochemical and cell biological properties of Caenorhabditis elegans tropomyosin (CeTM) and obtained evidence that CeTM is antagonistic to ADF/cofilin-dependent actin filament dynamics. We purified CeTM, actin, and UNC-60B (a muscle-specific ADF/cofilin isoform), all of which are derived from C. elegans, and showed that CeTM and UNC-60B bound to F-actin in a mutually exclusive manner. CeTM inhibited UNC-60B–induced actin depolymerization and enhancement of actin polymerization. Within isolated native thin filaments, actin and CeTM were detected as major components, whereas UNC-60B was present at a trace amount. Purified UNC-60B was unable to interact with the native thin filaments unless CeTM and other associated proteins were removed by high-salt extraction. Purified CeTM was sufficient to restore the resistance of the salt-extracted filaments from UNC-60B. In muscle cells, CeTM and UNC-60B were localized in different patterns. Suppression of CeTM by RNA interference resulted in disorganized actin filaments and paralyzed worms in wild-type background. However, in an ADF/cofilin mutant background, suppression of CeTM did not worsen actin organization and worm motility. These results suggest that tropomyosin is a physiological inhibitor of ADF/cofilin-dependent actin dynamics.

scholarly journals A genome-wide CRISPR cell growth screen identifies NCAPG as a new therapeutic target for hepatocellular carcinoma

2017 ◽  
Vol 28 ◽  
pp. vii14 ◽  
Author(s):  
Y. Wang ◽  
B. Gao ◽  
P.Y. Tan ◽  
Y.A. Handoko ◽  
K. Sekar ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Therapeutic Target ◽  
Genome Wide ◽  
A Genome

scholarly journals Crosstalk in oxygen homeostasis networks: SKN-1/NRF inhibits the HIF-1 hypoxia-inducible factor in Caenorhabditis elegans

2021 ◽  
Author(s):  
Dingxia Feng ◽  
Zhiwei Zhai ◽  
Zhiyong Shao ◽  
Yi Zhang ◽  
Jo Anne Powell-Coffman
Keyword(s):  
Oxidative Stress ◽  
Hypoxia Inducible Factor ◽  
Regulatory Sequences ◽  
Low Oxygen ◽  
Transcriptional Responses ◽  
C Elegans ◽  
Protein Levels ◽  
Oxygen Homeostasis ◽  
Genome Wide ◽  
A Genome

AbstractDuring development, homeostasis, and disease, organisms must balance responses that allow adaptation to low oxygen (hypoxia) with those that protect cells from oxidative stress. The evolutionarily conserved hypoxia-inducible factors are central to these processes, as they orchestrate transcriptional responses to oxygen deprivation. Here, we employ genetic strategies in C. elegans to identify stress-responsive genes and pathways that modulate the HIF-1 hypoxia-inducible factor and facilitate oxygen homeostasis. Through a genome-wide RNAi screen, we show that RNAi-mediated mitochondrial or proteasomal dysfunction increases the expression of hypoxia-responsive reporter Pnhr-57:GFP in C. elegans. Interestingly, only a subset of these effects requires hif-1. Of particular importance, we found that skn-1 RNAi increases the expression of hypoxia-responsive reporter Pnhr-57:GFP and elevates HIF-1 protein levels. The SKN-1/NRF transcription factor has been shown to promote oxidative stress resistance. We present evidence that the crosstalk between HIF-1 and SKN-1 is mediated by EGL-9, the prolyl hydroxylase that targets HIF-1 for oxygen-dependent degradation. Treatment that induces SKN-1, such as heat, increases expression of a Pegl-9:GFP reporter, and this effect requires skn-1 function and a putative SKN-1 binding site in egl-9 regulatory sequences. Collectively, these data support a model in which SKN-1 promotes egl-9 transcription, thereby inhibiting HIF-1. We propose that this interaction enables animals to adapt quickly to changes in cellular oxygenation and to better survive accompanying oxidative stress.

scholarly journals Control of ribosomal protein synthesis by Microprocessor complex

2020 ◽  
Author(s):  
Xuan Jiang ◽  
Amit Prabhakar ◽  
Stephanie M. Van der Voorn ◽  
Prajakta Ghatpande ◽  
Barbara Celona ◽  
...  
Keyword(s):  
Cell Growth ◽  
Nuclear Export ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Cellular Growth ◽  
New Paradigm ◽  
Erythroid Progenitors ◽  
Conditional Deletion ◽  
Microprocessor Complex ◽  
Ribosomal Protein Synthesis

AbstractRibosome biogenesis in eukaryotes requires stoichiometric production and assembly of 80 ribosomal proteins (RPs) and 4 ribosomal RNAs, and its rate must be coordinated with cellular growth. The indispensable regulator of RP biosynthesis is the 5’-terminal oligopyrimidine (TOP) motif, spanning the transcription start site of all RP genes. Here we show that the Microprocessor complex, previously linked to the first step of processing microRNAs (miRNAs), coregulates RP expression by binding the TOP motif of nascent RP mRNAs and stimulating transcription elongation via resolution of DNA/RNA hybrids. Cell growth arrest triggers nuclear export and degradation of the Microprocessor protein Drosha by the E3 ubiquitin ligase Nedd4, accumulation of DNA/RNA hybrids at RP gene loci, decreased RP synthesis, and ribosome deficiency, hence synchronizing ribosome production with cell growth. Conditional deletion of Drosha in erythroid progenitors phenocopies human ribosomopathies, in which ribosomal insufficiency leads to anemia. Outlining a miRNA-independent role of the Microprocessor complex at the interphase between cell growth and ribosome biogenesis offers a new paradigm by which cells alter their protein biosynthetic capacity and cellular metabolism.

HMGB proteins involved in TOR signaling as general regulators of cell growth by controlling ribosome biogenesis

2018 ◽  
Vol 64 (6) ◽  
pp. 1205-1213 ◽  
Author(s):  
A. Vizoso-Vázquez ◽  
A. Barreiro-Alonso ◽  
M. I. González-Siso ◽  
E. Rodríguez-Belmonte ◽  
M. Lamas-Maceiras ◽  
...  
Keyword(s):  
Cell Growth ◽  
Ribosome Biogenesis ◽  
Tor Signaling ◽  
Hmgb Proteins

scholarly journals The miR-26b-5p/KPNA2 Axis Is an Important Regulator of Burkitt Lymphoma Cell Growth

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1464
Author(s):  
Fubiao Niu ◽  
Marta Kazimierska ◽  
Ilja M. Nolte ◽  
Miente Martijn Terpstra ◽  
Debora de Jong ◽  
...  
Keyword(s):  
Cell Growth ◽  
Cell Lines ◽  
Burkitt Lymphoma ◽  
Target Genes ◽  
Fluorescent Protein ◽  
Luciferase Reporter ◽  
Argonaute 2 ◽  
A Genome ◽  
Green Fluorescent ◽  
Competition Assays

The expression of several microRNAs (miRNAs) is known to be changed in Burkitt lymphoma (BL), compared to its normal counterparts. Although for some miRNAs, a role in BL was demonstrated, for most of them, their function is unclear. In this study, we aimed to identify miRNAs that control BL cell growth. Two BL cell lines were infected with lentiviral pools containing either 58 miRNA inhibitors or 44 miRNA overexpression constructs. Eighteen constructs showed significant changes in abundance over time, indicating that they affected BL growth. The screening results were validated by individual green fluorescent protein (GFP) growth competition assays for fifteen of the eighteen constructs. For functional follow-up studies, we focused on miR-26b-5p, whose overexpression inhibited BL cell growth. Argonaute 2 RNA immunoprecipitation (Ago2-IP) in two BL cell lines revealed 47 potential target genes of miR-26b-5p. Overlapping the list of putative targets with genes showing a growth repression phenotype in a genome-wide CRISPR/Cas9 knockout screen, revealed eight genes. The top-5 candidates included EZH2, COPS2, KPNA2, MRPL15, and NOL12. EZH2 is a known target of miR-26b-5p, with oncogenic properties in BL. The relevance of the latter four targets was confirmed using sgRNAs targeting these genes in individual GFP growth competition assays. Luciferase reporter assay confirmed binding of miR-26b-5p to the predicted target site for KPNA2, but not to the other genes. In summary, we identified 18 miRNAs that affected BL cell growth in a loss- or gain-of-function screening. A tumor suppressor role was confirmed for miR-26b-5p, and this effect could at least in part be attributed to KPNA2, a known regulator of OCT4, c-jun, and MYC.

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