Search results for " Regulation"
showing 10 items of 3187 documents
Loss of ISWI Function in Drosophila Nuclear Bodies Drives Cytoplasmic Redistribution of Drosophila TDP-43
2018
Over the past decade, evidence has identified a link between protein aggregation, RNA biology, and a subset of degenerative diseases. An important feature of these disorders is the cytoplasmic or nuclear aggregation of RNA-binding proteins (RBPs). Redistribution of RBPs, such as the human TAR DNA-binding 43 protein (TDP-43) from the nucleus to cytoplasmic inclusions is a pathological feature of several diseases. Indeed, sporadic and familial forms of amyotrophic lateral sclerosis (ALS) and fronto-temporal lobar degeneration share as hallmarks ubiquitin-positive inclusions. Recently, the wide spectrum of neurodegenerative diseases characterized by RBPs functions’ alteration and loss was coll…
Transmembrane signaling and cytoplasmic signal conversion by dimeric transmembrane helix 2 and a linker domain of the DcuS sensor kinase
2020
Transmembrane (TM) signaling is a key process of membrane-bound sensor kinases. The C4-dicarboxylate (fumarate) responsive sensor kinase DcuS of Escherichia coli is anchored by TM helices TM1 and TM2 in the membrane. Signal transmission across the membrane relies on the piston-type movement of the periplasmic part of TM2. To define the role of TM2 in TM signaling, we use oxidative Cys cross-linking to demonstrate that TM2 extends over the full distance of the membrane and forms a stable TM homodimer in both the inactive and fumarate-activated state of DcuS. An S186xxxGxxxG194 motif is required for the stability and function of the TM2 homodimer. The TM2 helix further extends on the periplas…
The MRN complex is transcriptionally regulated by MYCN during neural cell proliferation to control replication stress
2015
The MRE11/RAD50/NBS1 (MRN) complex is a major sensor of DNA double strand breaks, whose role in controlling faithful DNA replication and preventing replication stress is also emerging. Inactivation of the MRN complex invariably leads to developmental and/or degenerative neuronal defects, the pathogenesis of which still remains poorly understood. In particular, NBS1 gene mutations are associated with microcephaly and strongly impaired cerebellar development, both in humans and in the mouse model. These phenotypes strikingly overlap those induced by inactivation of MYCN, an essential promoter of the expansion of neuronal stem and progenitor cells, suggesting that MYCN and the MRN complex migh…
Class I histone deacetylases regulate p53/NF-κB crosstalk in cancer cells
2016
The transcription factors NF-κB and p53 as well as their crosstalk determine the fate of tumor cells upon therapeutic interventions. Replicative stress and cytokines promote signaling cascades that lead to the co-regulation of p53 and NF-κB. Consequently, nuclear p53/NF-κB signaling complexes activate NF-κB-dependent survival genes. The 18 histone deacetylases (HDACs) are epigenetic modulators that fall into four classes (I-IV). Inhibitors of histone deacetylases (HDACi) become increasingly appreciated as anti-cancer agents. Based on their effects on p53 and NF-κB, we addressed whether clinically relevant HDACi affect the NF-κB/p53 crosstalk. The chemotherapeutics hydroxyurea, etoposide, an…
Longitudinal Investigation into Genetics in the Conservation of Metabolic Phenotypes in Danish and Chinese Twins
2016
Longitudinal twin studies on long term conservation of individual metabolic phenotypes can help to explore the genetic and environmental basis in maintaining metabolic homeostasis and metabolic health. We performed a longitudinal twin study on 12 metabolic phenotypes from Danish twins followed up for 12 years and Chinese twins traced for 7 years. The study covered a relatively large sample of 502 pairs of Danish adult twins with a mean age at intake of 38 years and a total of 181 Chinese adult twin pairs with a mean baseline age of 39.5 years. Bivariate twin models were fitted to the longitudinal measurements taken at two time points (at baseline and follow-up) to estimate the genetic and e…
Identification and characterization of durum wheat microRNAs in leaf and root tissues.
2017
MicroRNAs are a class of post-transcriptional regulators of plant developmental and physiological processes and responses to environmental stresses. Here, we present the study regarding the annotation and characterization of MIR genes conducted in durum wheat. We characterized the miRNAome of leaf and root tissues at tillering stage under two environmental conditions: irrigated with 100% (control) and 55% of evapotranspiration (early water stress). In total, 90 microRNAs were identified, of which 32 were classified as putative novel and species-specific miRNAs. In addition, seven microRNA homeologous groups were identified in each of the two genomes of the tetraploid durum wheat. Differenti…
DHA induces Jurkat T-cell arrest in G2/M phase of cell cycle and modulates the plasma membrane expression of TRPC3/6 channels.
2021
Abstract We investigated whether docosahexaenoic acid (DHA), a dietary n-3 fatty acid, modulates calcium (Ca2+) signaling and cell cycle progression in human Jurkat T-cells. Our study demonstrates that DHA inhibited Jurkat T-cell cycle progression by blocking their passage from S phase to G2/M phase. In addition, DHA decreased the plasma membrane expression of TRPC3 and TRPC6 calcium channels during T-cell proliferation. Interestingly, this fatty acid increased plasma membrane expression of TRPC6 after 24 h of mitogenic stimulation by phorbol-13-myristate-12-acetate (PMA) and ionomycin. These variations in the membrane expression of TRPC3 and TRPC6 channels were not directly correlated with…
Identification of novel drug resistance mechanisms by genomic and transcriptomic profiling of glioblastoma cells with mutation-activated EGFR.
2021
Abstract Aims Epidermal growth factor receptor (EGFR) is not only involved in carcinogenesis, but also in chemoresistance. We characterized U87.MGΔEGFR glioblastoma cells with constitutively active EGFR due to deletion at the ligand binding domain in terms of gene expression profiling and chromosomal aberrations. Wild-type U87.MG cells served as control. Materials and methods RNA sequencing and network analyses (Ingenuity Pathway Analysis) were performed to identify novel drug resistance mechanisms related to expression of mutation activated EGFR. Chromosomal aberrations were characterized by multicolor fluorescence in situ hybridization (mFISH) and array comparative genomic hybridization (…
Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes.
2016
Abstract Ethnopharmacological relevance Multidrug resistance (MDR) of cancer is often associated with the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP or ABCG2), in cancer cells, which facilitates the active efflux of a wide variety of chemotherapeutic drugs out of the cells. Marsdenia tenacissima is a traditional Chinese medicinal herb that has long been clinically used for treatment of cancers, particularly in combinational use with anticancer drugs. Polyoxypregnanes (POPs) are identified as main constituents of this herb, and three of them have been re…
Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury
2017
Drug-induced liver injury (DILI) has a considerable impact on human health and is a major challenge in drug safety assessments. DILI is a frequent cause of liver injury and a leading reason for post-approval drug regulatory actions. Considerable variations in the expression levels of both cytochrome P450 (CYP) and conjugating enzymes have been described in humans, which could be responsible for increased susceptibility to DILI in some individuals. We herein explored the feasibility of the combined use of HepG2 cells co-transduced with multiple adenoviruses that encode drug-metabolising enzymes, and a high-content screening assay to evaluate metabolism-dependent drug toxicity and to identify…