Search results for "Cyclin"
showing 10 items of 1021 documents
Aβ Induces Excitotoxicity Mediated by APC/C-Cdh1 Depletion That Can Be Prevented by Glutaminase Inhibition Promoting Neuronal Survival
2016
AbstractThe E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated by the fizzy-related protein homolog/CDC20-like protein 1 (cdh1) in post-mitotic neurons. Growing evidence suggests that dysregulation of APC/C-Cdh1 is involved in neurodegenerative diseases. Here we show in neurons that oligomers of amyloid beta (Aβ), a peptide related to Alzheimer’s disease, cause proteasome-dependent degradation of cdh1. This leads to a subsequent increase in glutaminase (a degradation target of APC/C-Cdh1), which causes an elevation of glutamate levels and further intraneuronal Ca2+ dysregulation, resulting in neuronal apoptosis. Glutaminase inhibition prevents glutamate excitotoxi…
Recent advances on CDK inhibitors: An insight by means of in silico methods
2017
The cyclin dependent kinases (CDKs) are a small family of serine/threonine protein kinases that can act as a potential therapeutic target in several proliferative diseases, including cancer. This short review is a survey on the more recent research progresses in the field achieved by using in silico methods. All the "armamentarium" available to the medicinal chemists (docking protocols and molecular dynamics, fragment-based, de novo design, virtual screening, and QSAR) has been employed to the discovery of new, potent, and selective inhibitors of cyclin dependent kinases. The results cited herein can be useful to understand the nature of the inhibitor-target interactions, and furnish an ins…
Whi7 is an unstable cell-cycle repressor of the Start transcriptional program
2017
Start is the main decision point in eukaryotic cell cycle in which cells commit to a new round of cell division. It involves the irreversible activation of a transcriptional program by G1 CDK-cyclin complexes through the inactivation of Start transcriptional repressors, Whi5 in yeast or Rb in mammals. Here we provide novel keys of how Whi7, a protein related at sequence level to Whi5, represses Start. Whi7 is an unstable protein, degraded by the SCFGrr1 ubiquitin-ligase, whose stability is cell cycle regulated by CDK1 phosphorylation. Importantly, Whi7 associates to G1/S gene promoters in late G1 acting as a repressor of SBF-dependent transcription. Our results demonstrate that Whi7 is a ge…
A comparative study of the degradation of yeast cyclins Cln1 and Cln2.
2016
The yeast cyclins Cln1 and Cln2 are very similar in both sequence and function, but some differences in their functionality and localization have been recently described. The control of Cln1 and Cln2 cellular levels is crucial for proper cell cycle initiation. In this work, we analyzed the degradation patterns of Cln1 and Cln2 in order to further investigate the possible differences between them. Both cyclins show the same half‐life but, while Cln2 degradation depends on ubiquitin ligases SCFG rr1 and SCFC dc4, Cln1 is affected only by SCFG rr1. Degradation analysis of chimeric cyclins, constructed by combining fragments from Cln1 and Cln2, identifies the N‐terminal sequence of the proteins…
Ecological network analysis reveals the inter-connection between soil biodiversity and ecosystem function as affected by land use across Europe
2016
Soil organisms are considered drivers of soil ecosystem services (primary productivity, nutrient cycling, carbon cycling, water regulation) associated with sustainable agricultural production. Soil biodiversity was highlighted in the soil thematic strategy as a key component of soil quality. The lack of quantitative standardised data at a large scale has resulted in poor understanding of how soil biodiversity could be incorporated into legislation for the protection of soil quality. In 2011, the EcoFINDERS (FP7) project sampled 76 sites across 11 European countries, covering five biogeographical zones (Alpine, Atlantic, Boreal, Continental and Mediterranean) and three land-uses (arable, gra…
Antibiotic Resistance Profiling, Analysis of Virulence Aspects and Molecular Genotyping of Staphylococcus aureus Isolated in Sicily, Italy
2018
Abstract Staphylococcus aureus is the major cause of foodborne diseases worldwide. In this retrospective study, 84 S. aureus strains were characterized. The collection comprises 78 strains isolated during 1998 and 2014 from dairy products and tissue samples from livestock bred for dairy production in Sicily. One isolate was obtained from a pet (dog), one from an exotic animal (a circus elephant), and four human isolates were obtained during a severe food poisoning outbreak that occurred in Sicily in 2015. All the strains were characterized by pulsed-field gel electrophoresis (PFGE), for antibiotic resistance and presence of toxin genes. PFGE results showed 10 different pulsotypes, with thre…
Evaluation of antimicrobial resistance and virulence of enterococci from equipment surfaces, raw materials and traditional cheeses
2016
Forty enterococci isolated along the production chains of three traditional cheeses (PDO Pecorino Siciliano, PDO Vastedda della Valle del Belìce, and Caciocavallo Palermitano) made in Sicily (southern Italy) were studied for the assessment of their antibiotic resistance and virulence by a combined phenotypic/genotypic approach. A total of 31 Enterococcus displayed resistance to at least one or more of the antimicrobials tested. The strains exhibited high percentages of resistance to erythromycin (52.5%), ciprofloxacin (35.0%), quinupristin–dalfopristin (20.0%), tetracycline (17.5%), and high-level streptomycin (5.0%). The presence of tet(M), cat(pC221), and aadE genes for resistance to tetr…
Molecular diagnostic of Ureaplasma urealyticum presence and tetracycline resistance in urine samples
2021
Abstract Sexually transmitted infections (STIs) are among the most common infections in Romania. Infection with Ureaplasma urelyticum is one of the major causes of STIs and can cause serious complications. Although tetracycline is the drug commonly used to treat infections caused by U. urealyticum, several studies indicate the emergence and rapid development of strains resistant to these antibiotics in the United States or Europe. Tetracycline resistance in bacteria is encoded by a number of different genetic determinants but in mycoplasmas the only tetracycline resistance determinant that has been reported is the tetM gene. Tetracycline resistance among Ureaplasma spp. is associated with t…
Peaks of in situ N2O emissions are influenced by N2O producing and reducing microbial communities across arable soils
2018
International audience; Introduction Agriculture is the main source of terrestrial N2O emissions, a potent greenhouse gas and the main cause of ozone depletion ((Hu et al., 2015). The reduction of N2O into N2 by microorganisms carrying the nitrous oxide reductase gene (nosZ) is the only known biological process eliminating this greenhouse gas. Recent studies showed that a previously unknown clade of N2O-reducers (nosZII) was related to the potential capacity of the soil to act as a N2O sink (see Hallin et al., 2017 and references therein). However little is known about how this group responds to different agricultural practices. Here, we investigated how N2O-producers and N2O-reducers were …
GDF11 exhibits tumor suppressive properties in hepatocellular carcinoma cells by restricting clonal expansion and invasion.
2019
Growth differentiation factor 11 (GDF11) has been characterized as a key regulator of differentiation in cells that retain stemness features, despite some controversies in age-related studies. GDF11 has been poorly investigated in cancer, particularly in those with stemness capacity, such as hepatocellular carcinoma (HCC), one of the most aggressive cancers worldwide. Here, we focused on investigating the effects of GDF11 in liver cancer cells. GDF11 treatment significantly reduced proliferation, colony and spheroid formation in HCC cell lines. Consistently, down-regulation of CDK6, cyclin D1, cyclin A, and concomitant upregulation of p27 was observed after 24 h of treatment. Interestingly,…