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https://www.readbyqxmd.com/read/28109176/oncogenic-roles-of-smarcb1-ini1-and-its-deficient-tumors
#1
Kenichi Kohashi, Yoshinao Oda
SMARCB1/INI1 is one of the core subunit proteins of the ATP-dependent SWI/SNF chromatin remodeling complex, and is identified as a potent and bona fide tumor suppressor. Interactions have been demonstrated between SMARCB1/INI1 and key proteins in various pathways related to tumor proliferation and progression: the p16-RB pathway, WNT signaling pathway, sonic hedgehog signaling pathway and Polycomb pathway. Initially, no detectable SMARCB1/INI1 protein expression was found in malignant rhabdoid tumor cells, whereas all other kinds of tumor cells and non-tumorous tissue showed SMARCB1/INI1 protein expression...
January 21, 2017: Cancer Science
https://www.readbyqxmd.com/read/28108764/letr-is-a-tetr-family-transcription-factor-from-lysobacter-controlling-antifungal-antibiotic-biosynthesis
#2
Ping Wang, Hongfu Chen, Guoliang Qian, Fengquan Liu
Heat-stable antifungal factor (HSAF) is a newly identified and broad-spectrum antifungal antibiotic from Lysobacter enzymogenes, a ubiquitous environmental proteobacterium. Yet, the regulatory mechanism for HSAF biosynthesis in L. enzymogenes remains poorly understood. Here, we report the identification of a TetR-family protein Le1552 (LetR) from L. enzymogenes strain OH11 that is involved in transcriptional repression of HSAF production. Bacterial one-hybrid and gel mobility shift assays show that LetR directly binds to PHSAF (the promoter region of the HSAF biosynthesis operon)...
January 20, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28108243/tpx2-as-a-prognostic-indicator-and-potential-therapeutic-target-in-clear-cell-renal-cell-carcinoma
#3
Zachary A Glaser, Harold D Love, Shunhua Guo, Lan Gellert, Sam S Chang, Stanley Duke Herrell, Daniel A Barocas, David F Penson, Michael S Cookson, Peter E Clark
OBJECTIVES: Our aims were to determine if targeting protein for Xklp2 (TPX2) is correlated with clear cell renal cell carcinoma (ccRCC) histology and oncologic outcomes using The Cancer Genome Atlas (TCGA) and an institutional tissue microarray (TMA). METHODS: Clinicopathological data obtained from the TCGA consisted of 415 samples diagnosed with ccRCC. A TMA was constructed from tumors of 207 patients who underwent radical nephrectomy for ccRCC. TPX2 expression by immunohistochemistry on TMA was assessed by a genitourinary pathologist...
January 17, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28104892/mechanistic-basis-for-a-molecular-triage-reaction
#4
Sichen Shao, Monica C Rodrigo-Brenni, Maryann H Kivlen, Ramanujan S Hegde
Newly synthesized proteins are triaged between biosynthesis and degradation to maintain cellular homeostasis, but the decision-making mechanisms are unclear. We reconstituted the core reactions for membrane targeting and ubiquitination of nascent tail-anchored membrane proteins to understand how their fate is determined. The central six-component triage system is divided into an uncommitted client-SGTA complex, a self-sufficient targeting module, and an embedded but self-sufficient quality control module. Client-SGTA engagement of the targeting module induces rapid, private, and committed client transfer to TRC40 for successful biosynthesis...
January 20, 2017: Science
https://www.readbyqxmd.com/read/28104713/multimerization-properties-of-piggymac-a-domesticated-piggybac-transposase-involved-in-programmed-genome-rearrangements
#5
Emeline Dubois, Nathalie Mathy, Vinciane Régnier, Julien Bischerour, Céline Baudry, Raphaëlle Trouslard, Mireille Bétermier
During sexual processes, the ciliate Paramecium eliminates 25-30% of germline DNA from its somatic genome. DNA elimination includes excision of ∼45 000 short, single-copy internal eliminated sequences (IESs) and depends upon PiggyMac (Pgm), a domesticated piggyBac transposase that is essential for DNA cleavage at IES ends. Pgm carries a core transposase region with a putative catalytic domain containing three conserved aspartic acids, and a downstream cysteine-rich (CR) domain. A C-terminal extension of unknown function is predicted to adopt a coiled-coil (CC) structure...
January 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28104453/alphavirus-polymerase-and-rna-replication
#6
REVIEW
Maija K Pietilä, Kirsi Hellström, Tero Ahola
Alphaviruses are typically arthropod-borne, and many are important pathogens such as chikungunya virus. Alphaviruses encode four nonstructural proteins (nsP1-4), initially produced as a polyprotein P1234. nsP4 is the core RNA-dependent RNA polymerase but all four nsPs are required for RNA synthesis. The early replication complex (RC) formed by the polyprotein P123 and nsP4 synthesizes minus RNA strands, and the late RC composed of fully processed nsP1-nsP4 is responsible for the production of genomic and subgenomic plus strands...
January 16, 2017: Virus Research
https://www.readbyqxmd.com/read/28104350/neonatal-exposure-to-bde-209-impaired-learning-and-memory-decreased-expression-of-hippocampal-core-snares-and-synaptophysin-in-adult-rats
#7
Xiong Li, Chunmei Wang, Wen Wang, Chengwei Yue, Yan Tang
Polybrominated diphenyl ethers (PBDEs) are a class of flame retardants. While the mechanism remains unknown, the potential neurotoxic effects of PBDEs remain a relevant issue. In the present study, neonatal Sprague-Dawley rats of both sexes were administered BDE 209 (1, 10, or 20mg/kg body weight) or peanut oil once daily from postnatal day (PND) 5 to PND 10. We examined the spatial learning and memory by Morris water maze and the working and reference memory by eight-arm radial maze in the stage of adulthood...
January 16, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28104305/cp39-cp75-and-cp91-are-major-structural-components-of-the-dictyostelium-centrosome-s-core-structure
#8
Irene Meyer, Tatjana Peter, Petros Batsios, Oliver Kuhnert, Anne Krüger-Genge, Carl Camurça, Ralph Gräf
The acentriolar Dictyostelium centrosome is a nucleus-associated body consisting of a core structure with three plaque-like layers, which are surrounded by a microtubule-nucleating corona. The core duplicates once per cell cycle at the G2/M transition, whereby its central layer disappears and the two outer layers form the mitotic spindle poles. Through proteomic analysis of isolated centrosomes, we have identified CP39 and CP75, two essential components of the core structure. Both proteins can be assigned to the central core layer as their centrosomal presence is correlated to the disappearance and reappearance of the central core layer in the course of centrosome duplication...
January 12, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28103675/genome-mining-of-amino-group-carrier-protein-mediated-machinery-discovery-and-biosynthetic-characterization-of-a-natural-product-with-unique-hydrazone-unit
#9
Kenichi Matsuda, Fumihito Hasebe, Yuh Shiwa, Yu Kanesaki, Takeo Tomita, Hirofumi Yoshikawa, Kazuo Shin-Ya, Tomohisa Kuzuyama, Makoto Nishiyama
We recently revealed that a Streptomyces strain possesses the gene encoding amino group carrier protein (AmCP). AmCP is involved in the biosynthesis of a previously unidentified nonproteinogenic amino acid, (2S,6R)-diamino-(5R,7)-dihydroxy-heptanoic acid (DADH), which is a core compound for the synthesis of the dipeptide-containing novel natural product vazabitide A. We used polymerase chain reaction (PCR) screening to investigate the diversity of the biosynthetic machinery that uses AmCP; the results revealed that genes encoding AmCP are widely distributed among actinomycetes...
January 20, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28103323/the-complete-genome-sequence-of-a-second-distinct-betabaculovirus-from-the-true-armyworm-mythimna-unipuncta
#10
Robert L Harrison, Daniel L Rowley, Joseph Mowery, Gary R Bauchan, David A Theilmann, George F Rohrmann, Martin A Erlandson
The betabaculovirus originally called Pseudaletia (Mythimna) sp. granulovirus #8 (MyspGV#8) was examined by electron microscopy, host barcoding PCR, and determination of the nucleotide sequence of its genome. Scanning and transmission electron microscopy revealed that the occlusion bodies of MyspGV#8 possessed the characteristic size range and morphology of betabaculovirus granules. Barcoding PCR using cytochrome oxidase I primers with DNA from the MyspGV#8 collection sample confirmed that it had been isolated from the true armyworm, Mythimna unipuncta (Lepidoptera: Noctuidae) and therefore was renamed MyunGV#8...
2017: PloS One
https://www.readbyqxmd.com/read/28103046/food-protein-based-core-shell-nanocarriers-for-oral-drug-delivery-effect-of-shell-composition-on-in-vitro-and-in-vivo-functional-performance-of-zein-nanocarriers
#11
Mohammed S Alqahtani, Md Saiful Islam, Satheesh Podaralla, Radhey S Kaushik, Joshua J Reineke, Tofuko Woyengo, Omathanu Perumal
The study was aimed at systematically investigating the influence of shell composition on the particle size, stability, release, cell uptake, permeability and in-vivo gastrointestinal distribution of food protein-based nanocarriers for oral delivery applications. Three different core-shell nanocarriers were prepared using food-grade biopolymers including zein-casein (ZC) nanoparticles, zein-lactoferrin (ZLF) nanoparticles and zein-PEG (ZPEG) micelles. Nile red was used as a model hydrophobic dye for in-vitro studies...
January 19, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28100844/phospholipids-and-products-of-their-hydrolysis-as-dietary-preventive-factors-for-civilization-diseases
#12
Karol Parchem, Agnieszka Bartoszek
The results of numerous epidemiological studies indicate that phospholipids play an important role in the prevention of chronic diseases faced by contemporary society. Firstly, these compounds are responsible for the proper functioning of cell membranes, by ensuring liquidity and permeability, which is pivotal for normal activity of membrane proteins, including receptors. These mechanisms are at the core of prevention of cancer, autoimmune or neurological disorders. Secondly, structure and properties of phospholipids cause that they are highly available source of biologically active fatty acids...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28100784/mitochondrial-o-glcnac-transferase-mogt-regulates-mitochondrial-structure-function-and-survival-in-hela-cells
#13
Juliana L Sacoman, Raul Y Dagda, Amanda R Burnham-Marusich, Ruben K Dagda, Patricia M Berninsone
O-linked N-acetylglucosamine transferase (OGT) catalyzes O-GlcNAcylation of target proteins and regulates numerous biological processes. OGT is encoded by a single gene that yields nucleocytosolic and mitochondrial isoforms. To date, the role of the mitochondrial isoform of OGT (mOGT) remains largely unknown. Using high-throughput proteomics, we identified 84 candidate mitochondrial glycoproteins, of which 44 are novel. Notably, two of the candidate glycoproteins identified (cytochrome oxidase 2 (COX2) and NADH: ubiquinone oxidoreductase core subunit 4 (MT-ND4)) are encoded by mitochondrial DNA...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28100692/insights-into-the-recq-helicase-mechanism-revealed-by-the-structure-of-the-helicase-domain-of-human-recql5
#14
Joseph A Newman, Hazel Aitkenhead, Pavel Savitsky, Opher Gileadi
RecQ helicases are important maintainers of genome integrity with distinct roles in almost every cellular process requiring access to DNA. RECQL5 is one of five human RecQ proteins and is particularly versatile in this regard, forming protein complexes with a diverse set of cellular partners in order to coordinate its helicase activity to various processes including replication, recombination and DNA repair. In this study, we have determined crystal structures of the core helicase domain of RECQL5 both with and without the nucleotide ADP in two distinctly different ('Open' and 'Closed') conformations...
January 18, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28100687/a-stripak-complex-mediates-axonal-transport-of-autophagosomes-and-dense-core-vesicles-through-pp2a-regulation
#15
Amanda L Neisch, Thomas P Neufeld, Thomas S Hays
Autophagy plays an essential role in the cellular homeostasis of neurons, facilitating the clearance of cellular debris. This clearance process is orchestrated through the assembly, transport, and fusion of autophagosomes with lysosomes for degradation. The motor protein dynein drives autophagosome motility from distal sites of assembly to sites of lysosomal fusion. In this study, we identify the scaffold protein CKA (connector of kinase to AP-1) as essential for autophagosome transport in neurons. Together with other core components of the striatin-interacting phosphatase and kinase (STRIPAK) complex, we show that CKA associates with dynein and directly binds Atg8a, an autophagosomal protein...
January 18, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28098447/the-stories-tryptophans-tell-exploring-protein-dynamics-of-heptosyltransferase-i-from-escherichia-coli
#16
Joy M Cote, Carlos Andres Ramirez-Mondragon, Zarek S Siegel, Daniel Joseph Czyzyk, Jiali Gao, Yuk Yin Sham, Ishita Mukerji, Erika A Taylor
Heptosyltransferase I (HepI) catalyzes the addition of a single L-glycero-β-D-manno-heptose sugar (heptose) onto the membrane incorporated Kdo2-Lipid A as part of the biosynthesis of the core region of lipopolysaccharide (LPS). Gram-negative bacteria with gene knockouts of HepI have reduced virulence with enhanced susceptibility to hydrophobic antibiotics, making design of inhibitors against HepI of interest. Previous studies have shown that HepI protein dynamics are partially rate limiting, and therefore disruption of protein dynamics might provide a new strategy for inhibiting HepI...
January 18, 2017: Biochemistry
https://www.readbyqxmd.com/read/28098232/crystal-structure-of-sec10-a-subunit-of-the-exocyst-complex
#17
Jianxing Chen, Atsushi Yamagata, Keiko Kubota, Yusuke Sato, Sakurako Goto-Ito, Shuya Fukai
The exocyst complex is a heterooctameric protein complex composed of Sec3, Sec5, Sec6, Sec8, Sec10, Sec15, Exo70 and Exo84. This complex plays an essential role in trafficking secretory vesicles to the plasma membrane through its interaction with phosphatidylinositol 4,5-bisphosphate and small GTPases. To date, the near-full-length structural information of each subunit has been limited to Exo70, although the C-terminal half structures of Sec6, Sec15 and Exo84 and the structures of the small GTPase-binding domains of Sec3, Sec5 and Exo84 have been reported...
January 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28097795/impaired-n-linked-glycosylation-of-uptake-and-efflux-transporters-in-human-nonalcoholic-fatty-liver-disease
#18
John D Clarke, Petr Novak, April D Lake, Rhiannon N Hardwick, Nathan J Cherrington
BACKGROUND & AIMS: N-linked glycosylation of proteins is critical for proper protein folding and trafficking to the plasma membrane. Drug transporters are one class of proteins that have reduced function when glycosylation is impaired. N-linked glycosylation of plasma proteins has also been investigated as a biomarker for several liver diseases, including non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to assess the transcriptomic expression of genes involved in protein processing and glycosylation, and to determine the glycosylation status of key drug transporters during human NAFLD progression...
January 18, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28097745/immature-core-protein-of-hepatitis-c-virus-induces-an-unfolded-protein-response-through-inhibition-of-erad-l-in-a-yeast-model-system
#19
Shota Takahashi, Naoko Sato, Junichi Kikuchi, Hideaki Kakinuma, Jun Okawa, Yukiko Masuyama, Singo Iwasa, Hayato Irokawa, Gi-Wook Hwang, Akira Naganuma, Michinori Kohara, Shusuke Kuge
The structural protein Core of hepatitis C virus (HCV), a cytosolic protein, induces endoplasmic reticulum (ER) stress and unfolded protein response (UPR) in hepatocytes, and is responsible for the pathogenesis of persistent HCV infection. Using yeast as a model system, we evaluated mechanisms underlying Core-induced interference of ER homeostasis and UPR, and found that UPR is induced by the immature Core (aa 1-191, Core191) but not by the mature Core (aa 1-177, Core177). Interestingly, Core191 inhibits both ERAD-L, a degradation system responsible for misfolded/unfolded proteins in the ER lumen, and ERAD-M, a degradation system responsible for proteins carrying a misfolded/unfolded region in the ER membrane...
January 18, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28096444/single-molecule-fret-rosetta-reveals-rna-structural-rearrangements-during-human-telomerase-catalysis
#20
Joseph W Parks, Kalli Kappel, Rhiju Das, Michael D Stone
Maintenance of telomeres by telomerase permits continuous proliferation of rapidly dividing cells, including the majority of human cancers. Despite its direct biomedical significance, the architecture of the human telomerase complex remains unknown. Generating homogeneous telomerase samples has presented a significant barrier to developing improved structural models. Here we pair single-molecule Förster resonance energy transfer (smFRET) measurements with Rosetta modeling to map the conformations of the essential telomerase RNA core domain within the active ribonucleoprotein...
February 2017: RNA
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