Search results for "Initiation factor"
showing 10 items of 32 documents
Evolutionary conserved role of eukaryotic translation factor eIF5A in the regulation of actin-nucleating formins
2017
AbstractElongation factor eIF5A is required for the translation of consecutive prolines, and was shown in yeast to translate polyproline-containing Bni1, an actin-nucleating formin required for polarized growth during mating. Here we show that Drosophila eIF5A can functionally replace yeast eIF5A and is required for actin-rich cable assembly during embryonic dorsal closure (DC). Furthermore, Diaphanous, the formin involved in actin dynamics during DC, is regulated by and mediates eIF5A effects. Finally, eIF5A controls cell migration and regulates Diaphanous levels also in mammalian cells. Our results uncover an evolutionary conserved role of eIF5A regulating cytoskeleton-dependent processes…
Time dependent expression of the blood biomarkers EIF2D and TOX in patients with schizophrenia
2019
Background During last years, there has been an intensive search for blood biomarkers in schizophrenia to assist in diagnosis, prognosis and clinical management of the disease. Methods In this study, we first conducted a weighted gene coexpression network analysis to address differentially expressed genes in peripheral blood from patients with chronic schizophrenia (n?=?30) and healthy controls (n?=?15). The discriminating performance of the candidate genes was further tested in an independent cohort of patients with first-episode schizophrenia (n?=?124) and healthy controls (n?=?54), and in postmortem brain samples (cingulate and prefrontal cortices) from patients with schizophrenia (n?=?3…
eIF5A facilitates translation termination globally and promotes the elongation of many non polyproline-specific tripeptide sequences
2017
Abstract eIF5A is an essential protein involved in protein synthesis, cell proliferation and animal development. High eIF5A expression is observed in many tumor types and has been linked to cancer metastasis. Recent studies have shown that eIF5A facilitates the translation elongation of stretches of consecutive prolines. Activated eIF5A binds to the empty E-site of stalled ribosomes, where it is thought to interact with the peptidyl-tRNA situated at the P-site. Here, we report a genome-wide analysis of ribosome stalling in Saccharomyces cerevisiae eIF5A depleted cells using 5Pseq. We confirm that, in the absence of eIF5A, ribosomes stall at proline stretches, and extend previous studies by …
Inappropriate translation inhibition and P-body formation cause cold-sensitivity in tryptophan-auxotroph yeast mutants
2017
In response to different adverse conditions, most eukaryotic organisms, including Saccharomyces cerevisiae, downregulate protein synthesis through the phosphorylation of eIF2α (eukaryotic initiation factor 2α) by Gcn2, a highly conserved protein kinase. Gcn2 also controls the translation of Gcn4, a transcription factor involved in the induction of amino acid biosynthesis enzymes. Here, we have studied the functional role of Gcn2 and Gcn2-regulating proteins, in controlling translation during temperature downshifts of TRP1 and trp1 yeast cells. Our results suggest that neither cold-instigated amino acid limitation nor Gcn2 are involved in the translation suppression at low temperature. Howev…
Effects of muscular dystrophy, exercise and blocking activin receptor IIB ligands on the unfolded protein response and oxidative stress
2016
Protein homeostasis in cells, proteostasis, is maintained through several integrated processes and pathways and its dysregulation may mediate pathology in many diseases including Duchenne muscular dystrophy (DMD). Oxidative stress, heat shock proteins, endoplasmic reticulum (ER) stress and its response, i.e. unfolded protein response (UPR), play key roles in proteostasis but their involvement in the pathology of DMD are largely unknown. Moreover, exercise and activin receptor IIB blocking are two strategies that may be beneficial to DMD muscle, but studies to examine their effects on these proteostasis pathways are lacking. Therefore, these pathways were examined in the muscle of mdx mice, …
Cryptotanshinone deregulates unfolded protein response and eukaryotic initiation factor signaling in acute lymphoblastic leukemia cells.
2015
Abstract Background: Unfolded protein responses (UPR) determine cell fate and are recognized as anticancer targets. In a previous research, we reported that cryptotanshinone (CPT) exerted cytotoxic effects toward acute lymphoblastic leukemia cells through mitochondria-mediated apoptosis. Purpose: In the present study, we further investigated the role of UPR in CPT-induced cytotoxicity on acute lymphoblastic leukemia cells by applying tools of pharmacogenomics and bioinformatics. Methods: Gene expression profiling was performed by mRNA microarray hybridization. Potential transcription factor binding motifs were identified in the promoter regions of the deregulated genes by Cistrome software.…
Combination of osteopontin and activated leukocyte cell adhesion molecule as potent prognostic discriminators in HER2- and ER-negative breast cancer.
2010
Background: To analyse the discriminative impact of osteopontin (OPN) and activated leukocyte cell adhesion molecule (ALCAM), combined with human epidermal growth factor 2 (HER2) and oestrogen receptor (ER) in breast cancer. Methods: Osteopontin, ALCAM, HER2 and ER mRNA expression in breast cancer tissues of 481 patients were analysed (mRNA microarray analysis, kinetic RT–PCR). Hierarchical clustering was performed in training cohort A (N=100, adjuvant treatment) and validation cohorts B (N=200, no adjuvant treatment, low-risk) and C (N=181, adjuvant treatment, high-risk). Results: Negative/low ER and HER2, high OPN and low ALCAM mRNA expression helped to identify patients at particularly h…
Cellular stress induces cap-independent alpha-enolase/MBP-1 translation.
2015
AbstractMyc promoter-binding protein-1 (MBP-1) is a shorter protein variant of the glycolytic enzyme alpha-enolase. Although several lines of evidence indicate that MBP-1 acts as a tumor suppressor, the cellular mechanisms and signaling pathways underlying MBP-1 expression still remain largely elusive. To dissect these pathways, we used the SkBr3 breast cancer cell line and non-tumorigenic HEK293T cells ectopically overexpressing alpha-enolase/MBP-1. Here, we demonstrate that induced cell stresses promote MBP-1 expression through the AKT/PERK/eIF2α signaling axis. Our results contribute to shedding light on the molecular mechanisms underlying MBP-1 expression in non-tumorigenic and cancer c…
Early adaptive response of the retina to a pro-diabetogenic diet: Impairment of cone response and gene expression changes in high-fructose fed rats
2015
The lack of plasticity of neurons to respond to dietary changes, such as high fat and high fructose diets, by modulating gene and protein expression has been associated with functional and behavioral impairments that can have detrimental consequences. The inhibition of high fat-induced rewiring of hypothalamic neurons induced obesity. Feeding rodents with high fructose is a recognized and widely used model to trigger obesity and metabolic syndrome. However the adaptive response of the retina to short term feeding with high fructose is poorly documented. We therefore aimed to characterize both the functional and gene expression changes in the neurosensory retina of Brown Norway rats fed duri…
Yeast mRNA cap-binding protein Cbc1/Sto1 is necessary for the rapid reprogramming of translation after hyperosmotic shock.
2011
Global translation is inhibited in Saccharomyces cerevisiae cells under osmotic stress; nonetheless, osmostress-protective proteins are synthesized. We found that translation mediated by the mRNA cap-binding protein Cbc1 is stress-resistant and necessary for the rapid translation of osmostress-protective proteins under osmotic stress.