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00:39 EDT 21st September 2019 | BioPortfolio

The US National Library of Medicine and National Institutes of Health manage PubMed.gov which comprises of more than 29 million records, papers, reports for biomedical literature, including MEDLINE, life science and medical journals, articles, reviews, reports and  books.

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For example view all recent relevant publications on Epigenetics and associated publications and clincial trials.

Showing PubMed Articles 1–25 of 501 from FEBS letters

Soluble klotho regulates bone differentiation by upregulating expression of the transcription factor EGR-1.

Klotho is a transmembrane protein known to regulate aging and lifespan. Soluble klotho (sKl), a truncated form of klotho, regulates various cell signaling pathways, including bone development. Here, we investigated the relationship between sKl and the zinc-finger transcription factor early growth response protein 1 (EGR-1) on bone formation. We find that sKl induces the expression of EGR-1 mRNA and protein. Through mutational analysis, we identify the 130 bp region on the EGR-1 promoter that is responsive t...

Type 2 diabetes differentially affects the substrate saturation kinetic attributes of erythrocyte hexokinase and phosphofructokinase.

The substrate kinetic parameters of hexokinase and phosphofructokinase - the key irreversible enzymes of glycolysis - in erythrocytes from type 2 diabetic subjects were examined in comparison with control subjects. It was observed that the kinetic parameters such as Km, Vmax, Apparent Kcat, Kcat/Km and substrate (ATP) inhibition kinetics and substrate binding characteristics are significantly altered in the diabetic group. The observed changes are suggestive of compositional changes in the subunit make-up...

Human induced pluripotent stem cell-derived blood products: state of the art and future directions.

In vitro cultured blood cells for transfusion purposes provide a safe alternative to donor blood, particularly for patients that require recurrent transfusions, and can be used as carriers of therapeutic molecules. In vitro derivation of hematopoietic cell types from human induced pluripotent stem cells (iPSCs) allows for a constant, well defined production pipeline for such advanced therapeutic and medicinal products. Application of selected iPSC-derived hematopoietic stem cells and hematopoietic effector ...

Crystal structure of peptide-bound neprilysin reveals key binding interactions.

Neprilysin (NEP) is a promiscuous zinc metalloprotease with a broad substrate specificity and cleaves a remarkable diversity of substrates through endopeptidase action. Two of these - amyloid-β and natriuretic peptides - implicate the enzyme in both Alzheimer's disease and cardiovascular disease, respectively. Here, we report the creation of a catalytically inactive NEP (E584D) to determine the first peptide-bound crystal structure at 2.6 Å resolution. The structure reveals key interactions involved in su...

Closed fumarase C active site structures reveal SS Loop residue contribution in catalysis.

Fumarase C catalyzes the reversible conversion of fumarate to S-malate. Previous structural investigations within the superfamily have reported a dynamic structural segment, termed the SS Loop. To date, active site asymmetry has raised the question of how SS Loop placement affects participation of key residues during the reaction. Herein, we report structural and kinetic analyses from E. coli fumarase C variants to understand the contribution of SS Loop residues S318, K324 and N326. High-resolution X-ray cr...

N-glycome signatures in human plasma: associations with physiology and major diseases.

N-glycome analysis in total plasma or serum yields information about the levels and glycosylation patterns of major plasma glycoproteins, including immunoglobulins, acute-phase proteins and apolipoproteins. Until recently, glycomic studies in disease settings largely suffered from small cohort sizes, poor analytical resolution, and poor comparability of results owing to the diversity of analytical techniques. Here, we report on recent advances in high-throughput mass spectrometry glycomics technology that e...

Multiple functions of DYRK2 in cancer and tissue development.

Dual-specificity tyrosine-regulated kinases (DYRKs) are evolutionarily conserved from yeast to mammals. Accumulating studies have revealed that DYRKs have important roles in regulation of the cell cycle and survival. DYRK2, a member of the class II DYRK family protein, is a key regulator of p53, and phosphorylates it at Ser46 to induce apoptosis in response to DNA damage. Moreover, recent studies have uncovered that DYRK2 regulates G1/S transition, epithelial-mesenchymal-transition (EMT), and stemness in hu...

Getting out of mitosis: spatial and temporal control of mitotic exit and cytokinesis by PP1 and PP2A.

Here we will review the evidence showing that mitotic exit is initiated by regulated proteolysis and then driven by the PPP-family of phosphoserine/threonine phosphatases. Rapid APC/C and ubiquitin-dependent proteolysis of cyclin B and securin initiates sister chromatid separation, the first step of mitotic exit. Because proteolysis of Aurora and Polo family kinases dependent on APC/C is relatively slow, this creates a new regulatory state, anaphase, different to G2 and M-phase. We will discuss how the CDK1...

N-acetylglucosaminyltransferase I promotes glioma cell proliferation and migration through increasing the stability of the glucose transporter GLUT1.

Abnormal alteration of N-glycosylation structure contributes to glioma progression. N-acetylglucosaminyltransferase I (MGAT1) plays an essential role in the conversion of processed high-mannose cores into complex or hybrid N-linked oligosaccharide structures. The function of MGAT1 in glioma development remains largely unknown. Here, we found that the expression of MGAT1 is higher in glioblastoma compared to normal brain tissues. Inhibition of EGFR signaling pathway or serum starvation reduces MGAT1 expressi...

Localization and ER membrane insertion of parathyroid hormone-related protein analyzed without effects of reporter proteins.

Parathyroid hormone-related protein (PTHrP) is transported to both the secretory pathway and the nucleus/nucleolus by its dual targeting signals, that is, an N-terminal signal peptide and nuclear targeting signal. Curiously, reporter proteins such as EGFP strongly affect the localization of the fusion protein. Here, we report a novel methionine tag for S-labeling added to the C-terminus of its prepro-form, which has no methionine and cysteine residue other than the initiation methionine, that enables analy...

Proteins required for vacuolar function are targets of lysine polyphosphorylation in yeast.

Polyphosphates (polyP) are long chains of inorganic phosphates that can be attached to lysine residues of target proteins as a non-enzymatic post-translational modification. This modification, termed polyphosphorylation, may be particularly prevalent in bacterial and fungal species that synthesize large quantities of polyP. In this study, we evaluated the polyphosphorylation status of over 200 candidate targets in S. cerevisiae. We report 8 new polyphosphorylated proteins that interact genetically and physi...

Biochemical pathway for the biosynthesis of the Cu center in bacterial cytochrome c oxidase.

The di-copper center Cu is an essential metal cofactor in cytochrome oxidase of mitochondria and many prokaryotes, mediating one-electron transfer from cytochrome c to the site for oxygen reduction. Cu is located in subunit II (CoxB) of cytochrome oxidase and protrudes into the periplasm of Gram-negative bacteria or the mitochondrial intermembrane space. How the two copper ions are brought together to build CoxB·Cu is the subject of this review. It had been known that the reductase TlpA and the metallochap...

PsbS-Dependent and -Independent Mechanisms Regulate Carotenoid-Chlorophyll Energy Coupling in Grana Thylakoids.

In higher plants, PsbS is known to play a key role in the regulation of photosynthetic light-harvesting. However, the molecular mechanism and role of electronic carotenoid- chlorophyll (Chl) interactions for the down-regulation of excess excitation (non-photochemical energy quenching, NPQ) are still poorly understood. Here, we explored carotenoid → Chl energy transfer in isolated grana thylakoid membranes from mutants either deficient in or overexpressing PsbS. Since it was suggested that PsbS regulates t...

Increased Mistranslation Protects E. coli from Protein Misfolding Stress due to Activation of a RpoS-dependent Heat Shock Response.

The misincorporation of an incorrect amino acid into a polypeptide during protein synthesis is considered a detrimental phenomenon. A mistranslated protein is often misfolded and degraded or non-functional and results in an increased cost to quality control machinery. Despite these costs, errors during protein synthesis are common in bacteria. Here, we report that mistranslation in Escherichia coli increase the protein level of the heat shock sigma factor RpoH and protect cells against heat stress. Surprisi...

Adenovirus persistence, reactivation and clinical management.

Adenoviral infections continue posing a major threat in severely immunocompromised patients including particularly allogeneic stem cell transplant recipients. Although exogenous infections occur in some instances, the majority of invasive events appear to arise from viral reactivation. In the pediatric setting, adenoviruses were demonstrated to persist in the gastrointestinal tract, and the intestinal epithelium serves as the main site of viral replication preceding invasive infection. Regular monitoring of...

From and to the Golgi: Defining the Wilson disease protein road map.

Recent studies highlight the continued growth in the identification of a variety of cellular functions that involve the Golgi apparatus. Apart from well-known membrane sorting/trafficking and glycosylation machineries, the Golgi harbors molecular platforms operating in intracellular signaling, cytoskeleton organization, and protein quality control mechanisms. One of new emerging Golgi functions consists in the regulation of copper homeostasis by coordinating the relocation and activity of copper transporter...

Clustering in the Golgi apparatus governs sorting and function of GPI-APs in polarized epithelial cells.

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are lipid-anchored proteins attached to the extracellular leaflet of the plasma membrane via a glycolipid anchor. GPI-APs are commonly associated with cholesterol- and sphingolipid-enriched membrane microdomains. These microdomains help regulating various biological activities, by segregating different proteins and lipids in (nanoscale) membrane compartments. In fibroblasts, GPI-APs form actin- and cholesterol-dependent nanoclusters directly at the pl...

Ypt/Rab GTPases and their TRAPP GEFs at the Golgi.

The conserved Ypt/Rab GTPases regulate the different steps of all intracellular trafficking pathways. Ypt/Rabs are activated by their specific nucleotide exchangers termed GEFs, and when GTP-bound they recruit their downstream effectors, which mediate vesicular transport sub-steps. In the yeast exocytic pathway, Ypt1 and Ypt31/32 regulate traffic through the Golgi and the conserved modular TRAPP complex acts a GEF for both Ypt1 and Ypt31/32. However, the precise localization and function of these Ypts have ...

Trimeric structure of the mouse Kupffer cell C-type lectin receptor Clec4f.

The C-type lectin receptor Clec4f has been identified as a specific surface marker for Kupffer cells, though its ortholog is absent in humans and its biological function remains elusive. Here, we report the crystal structure of a truncated mouse trimeric Clec4f. The orientation between the carbohydrate-recognition domain of Clec4f and its neck region differs from other C-type lectins, resulting in an observed distance of 45 Å between the glycan binding sites within the Clec4f trimer. Interestingly, the tri...

Structural insights into the design of indole derivatives as tubulin polymerization inhibitors.

Microtubules are composed of αβ-tubulin heterodimers, and drugs that interfere with microtubule dynamics are used widely in cancer chemotherapy. Small synthetic molecules with an indole nucleus as a core structure have been identified as microtubule inhibitors and recognized as anticancer agents. However, structural information for the interactions between indole derivatives and tubulin is sparse. Here, we present the 2.55 Å crystal structure of tubulin in complex with the indole derivative D64131. We co...

Structure-guided design of immunomodulatory RNAs specifically targeting the cytoplasmic viral RNA sensor RIG-I.

The cytoplasmic immune sensor RIG-I detects viral RNA and initiates an antiviral immune response upon activation. It has become a potential target for vaccination and immunotherapies. To develop the smallest but potent immunomodulatory RNA (immRNAs) species, we performed structure-guided RNA design and used biochemical, structural and cell-based methods to select and characterize the immRNAs. We demonstrate that inserting guanosine at position 9 to the 10mer RNA hairpin (3p10LG9) activates RIG-I more robust...

The E3 ubiquitin ligase UBR5 interacts with the H/ACA ribonucleoprotein complex and regulates ribosomal RNA biogenesis in embryonic stem cells.

UBR5 is an E3 ubiquitin ligase involved in distinct processes such as transcriptional regulation and development. UBR5 is highly upregulated in embryonic stem cells (ESCs), whereas its expression decreases with differentiation, suggesting a role for UBR5 in ESC function. However, little is known about how UBR5 regulates ESC identity. Here, we define the protein interactome of UBR5 in ESCs and find interactions with distinct components of the H/ACA ribonucleoprotein complex, which is required for proper matu...

Bromhexine elevates REP2 expression to stimulate secretion from human primary conjunctiva fornix epithelial cells.

Bromhexine was reported to relieve the symptoms of Sjogren Syndrome at an early stage. However, the underlying mechanism remains unclear. Here, we administered bromhexine at low doses in human primary conjunctival fornix epithelial cells, and found it stimulated MUC5AC secretion and lipid droplet production. Expression of the metabolism-related gene CHML was also upregulated by bromhexine treatment, and REP2, the protein produced by the CHML gene, was induced. These results suggest that bromhexine is a pote...

Investigation of calmodulin-like and rod domain mutations suggests common molecular mechanism for α-actinin-1-linked congenital macrothrombocytopenia.

Actinin-1 mutations cause dominantly-inherited congenital macrothrombocytopenia (CMTP), with mutations in the actin-binding domain increasing actinin's affinity for F-actin. In this study, we examined nine CMTP-causing mutations in the calmodulin-like and rod domains of actinin-1. These mutations increase, to varying degrees, actinin's ability to bundle actin filaments in vitro. Mutations within the calmodulin-like domain decrease its thermal stability slightly but do not dramatically affect calcium binding...

Phosphatidic acid in membrane rearrangements.

Phosphatidic acid (PA) is the simplest cellular glycerophospholipid characterized by unique biophysical properties: a small headgroup; negative charge; and a phosphomonoester group. Upon interaction with lysine or arginine, PA charge increases from -1 to -2 and this change stabilizes protein-lipid interactions The biochemical properties of PA also allow interactions with lipids in several subcellular compartments. Based on this feature, PA is involved in the regulation and amplification of many cellular sig...


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