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https://www.readbyqxmd.com/read/29150959/nono-ubiquitination-is-mediated-by-fbw7-and-gsk3-%C3%AE-via-a-degron-lost-upon-chromosomal-rearrangement-in-cancer
#1
Luigi Alfano, Antonella Caporaso, Angela Altieri, Caterina Costa, Iris M Forte, Carmelina A Iannuzzi, Daniela Barone, Luca Esposito, Antonio Giordano, Francesca Pentimalli
NONO is an RNA-binding protein involved in transcription, mRNA splicing, DNA repair and checkpoint activation in response to UV radiation. NONO expression has been found altered in several tumour types, including prostate, colon, breast, melanoma and in papillary renal carcinoma, in which an X chromosome inversion generates a NONO-TFE3 fusion protein. Upon such rearrangement, NONO loses its C-terminal domain. Through bioinformatics analysis, we identified a putative degron motif, known to be recognized by the Skp1-Cul1-F-box-protein (SCF) complex...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150427/delayed-encounter-of-parental-genomes-can-lead-to-aneuploidy-in-saccharomyces%C3%A2-cerevisiae
#2
Alan Michael Tartakoff, David Dulce, Elizabeth Landis
We have investigated an extreme deviation from the norm of genome unification that occurs during mating in the yeast, Saccharomyces cerevisiae This deviation is encountered when yeast that carry a mutation of the spindle pole body protein, Kar1, are mated with wildtype cells. In this case, nuclear fusion is delayed and the genotypes of a fraction of zygotic progeny suggest that chromosomes have "transferred" between the parental nuclei in zygotes. This classic yet bizarre occurrence is routinely used to generate aneuploid (disomic) yeast...
November 17, 2017: Genetics
https://www.readbyqxmd.com/read/29149504/mybl1-rearrangements-and-myb-amplification-in-breast-adenoid-cystic-carcinomas-lacking-the-myb-nfib-fusion-gene
#3
Jisun Kim, Felipe C Geyer, Luciano G Martelotto, Charlotte K Y Ng, Raymond S Lim, Pier Selenica, Anqi Li, Fresia Pareja, Nicola Fusco, Marcia Edelweiss, Rahul Kumar, Rodrigo Gularte-Merida, Andre N Forbes, Ekta Khurana, Odette Mariani, Sunil Badve, Anne Vincent-Salomon, Larry Norton, Jorge S Reis-Filho, Britta Weigelt
Breast adenoid cystic carcinoma (AdCC), a rare type of triple-negative breast cancer (TNBC), has been shown to be driven by MYB pathway activation, most often underpinned by the MYB-NFIB fusion gene. Alternative genetic mechanisms, such as MYBL1 rearrangements, have been reported in MYB-NFIB-negative salivary gland AdCCs. Here we report on the molecular characterization by massively parallel sequencing of four breast AdCCs lacking the MYB-NFIB fusion gene. In two cases, we identified MYBL1 rearrangements (MYBL1-ACTN1 and MYBL1-NFIB), which were associated with MYBL1 overexpression...
November 17, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/29148922/feasibility-and-safety-of-using-thoracic-and-lumbar-cortical-bone-trajectory-pedicle-screws-in-spinal-constructs-in-children-technical-note
#4
Jonathan N Sellin, Jeffrey S Raskin, Kristen A Staggers, Alison Brayton, Valentina Briceño, Amee J Moreno, Andrew Jea
Thoracic and lumbar cortical bone trajectory pedicle screws have been described in adult spine surgery. They have likewise been described in pediatric CT-based morphometric studies; however, clinical experience in the pediatric age group is limited. The authors here describe the use of cortical bone trajectory pedicle screws in posterior instrumented spinal fusions from the upper thoracic to the lumbar spine in 12 children. This dedicated study represents the initial use of cortical screws in pediatric spine surgery...
November 17, 2017: Journal of Neurosurgery. Pediatrics
https://www.readbyqxmd.com/read/29148062/flagellar-incorporation-of-proteins-follows-at-least-two-different-routes-in-trypanosomes
#5
Laetitia Vincensini, Thierry Blisnick, Eloïse Bertiaux, Sebastian Hutchinson, Christina Georgikou, Cher-Pheng Ooi, Philippe Bastin
BACKGROUND INFORMATION: Eukaryotic cilia and flagella are sophisticated organelles composed of several hundreds of proteins that need to be incorporated at the right time and the right place during assembly. RESULTS: Two methods were used to investigate this process in the model protist Trypanosoma brucei: inducible expression of epitope-tagged labelled proteins and fluorescence recovery after photobleaching (FRAP) of fluorescent fusion proteins. This revealed that skeletal components of the radial spokes (RSP3), the central pair (PF16) and the outer dynein arms (DNAI1) are incorporated at the distal end of the growing flagellum...
November 16, 2017: Biology of the Cell
https://www.readbyqxmd.com/read/29147487/a-study-on-the-immune-response-induced-by-a-dna-vaccine-encoding-mtb32c-hbha-antigen-of-mycobacterium-tuberculosis
#6
Roghayeh Teimourpour, Hadi Peeridogaheh, Amir Teimourpour, Mohsen Arzanlou, Zahra Meshkat
Objectives: Tuberculosis (TB) has still remained a global health issue. One third of the world's population is infected with tuberculosis and the current BCG vaccine has low efficiency; hence, it is necessary to develop a new vaccine against TB. The aim of the current study was to evaluate the efficiency of a novel DNA vaccine encoding Mtb32C-HBHA antigen in inducing specific immune responses against Mycobacterium tuberculosis. Materials and Methods: A DNA plasmid vaccine expressing Mtb32C-HBHA fusion protein was constructed and its ability in protein expression was examined by RT-PCR and Western blot methods...
October 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29146937/tfeb-regulates-lysosomal-positioning-by-modulating-tmem55b-expression-and-jip4-recruitment-to-lysosomes
#7
Rose Willett, José A Martina, James P Zewe, Rachel Wills, Gerald R V Hammond, Rosa Puertollano
Lysosomal distribution is linked to the role of lysosomes in many cellular functions, including autophagosome degradation, cholesterol homeostasis, antigen presentation, and cell invasion. Alterations in lysosomal positioning contribute to different human pathologies, such as cancer, neurodegeneration, and lysosomal storage diseases. Here we report the identification of a novel mechanism of lysosomal trafficking regulation. We found that the lysosomal transmembrane protein TMEM55B recruits JIP4 to the lysosomal surface, inducing dynein-dependent transport of lysosomes toward the microtubules minus-end...
November 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/29146205/pax3-foxo1-zooming-in-on-an-undruggable-target
#8
REVIEW
Marco Wachtel, Beat W Schäfer
Driver oncogenes are prime targets for therapy in tumors many of which, including leukemias and sarcomas, express recurrent fusion transcription factors. One specific example for such a cancer type is alveolar rhabdomyosarcoma, which is associated in the majority of cases with the fusion protein PAX3-FOXO1. Since fusion transcription factors are challenging targets for development of small molecule inhibitors, indirect inhibitory strategies for this type of oncogenes represent a more promising approach. One can envision strategies at different molecular levels including upstream modifiers and activators, epigenetic and transcriptional co-regulators, and downstream effector targets...
November 13, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/29146117/implications-of-disturbances-in-circadian-rhythms-for-cardiovascular-health-a-new-frontier-in-free-radical-biology
#9
REVIEW
Neelam Khaper, Craig D C Bailey, Nilesh R Ghugre, Cristine Reitz, Zikra Awosanmi, Ryan Waines, Tami A Martino
Cell autonomous circadian "clock" mechanisms are present in virtually every organ, and generate daily rhythms that are important for normal physiology. This is especially relevant to the cardiovascular system, for example the circadian mechanism orchestrates rhythms in heart rate, blood pressure, cardiac contractility, metabolism, gene and protein abundance over the 24-hour day and night cycles. Conversely, disturbing circadian rhythms (e.g. via shift work, sleep disorders) increases cardiovascular disease risk, and exacerbates cardiac remodelling and worsens outcome...
November 13, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29145829/effect-of-a-rare-genetic-variant-of-tm7sf4-gene-on-osteoclasts-of-patients-with-paget-s-disease-of-bone
#10
Emilie Laurier, Nathalie Amiable, Edith Gagnon, Jacques P Brown, Laëtitia Michou
BACKGROUND: Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) is involved in osteoclastogenesis with a key role in mononucleated osteoclasts fusion. We reported in patients with Paget's disease of bone (PDB) a rare variant (rs62620995) in the TM7SF4 gene, encoding for DC-STAMP, which changes a highly conserved amino acid, possibly damaging according to in silico predictions. This study aimed at determining the functional effects of this variant on osteoclast phenotype in PDB. METHODS: Fifty ml of peripheral blood were collected in pagetic patients carrier of this variant (n = 4) or not (n = 4) and healthy controls (n = 4)...
November 16, 2017: BMC Medical Genetics
https://www.readbyqxmd.com/read/29144987/benzo-a-pyren-7-8-dihydrodiol-9-10-epoxide-induces-human-trophoblast-swan-71-cell-dysfunctions-due-to-cell-apoptosis-through-disorder-of-mitochondrial-fission-fusion
#11
Weiping Wang, Rong Wang, Qiao Zhang, Gil Mor, Huidong Zhang
Benzo(a)pyren-7,8-dihydrodiol-9,10-epoxide (BPDE) is an endocrine disrupter and ultimate carcinogenic product of benzo(a)pyrene (BaP). Numerous studies have shown that BPDE causes trophoblast-related diseases, such as preeclampsia, growth restriction or miscarriages. However, the underlying mechanism, especially the mitochondria-related BPDE-induced trophoblast dysfunction remains unknown. In this study, we examined mitochondrial functions in BPDE-induced human trophoblast cell line Swan 71. BPDE decreased cell ability, attenuated cell invasion and HCG secretion, induced cell apoptosis, decreased mitochondrial membrane potential, increased reactive oxygen species (ROS) and MDA, and decreased SOD activity in a dose-dependent manner...
November 13, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/29144506/soluble-p-selectin-promotes-retinal-ganglion-cell-survival-through-activation-of-nrf2-signaling-after-ischemia-injury
#12
Kishan Kapupara, Yao-Tseng Wen, Rong-Kung Tsai, Shun-Ping Huang
Retinal ischemic injuries play an important role in the pathogenesis of several eye disorders. Inflammation and oxidative stress are key players in ischemic injuries. Following retinal ischemia, vascular endothelial cells and leukocytes express several inflammatory adhesion receptors, such as selectins and cell adhesion molecules. P-selectin stimulates leukocyte recruitment to platelet aggregates and has an important role in vascular homeostasis and inflammatory leukocyte extravasation. Soluble P-selectin can be neuroprotective through competitive binding to the receptors of endogenous P-selectin molecules...
November 16, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29143881/rmce-based-insect-cell-platform-to-produce-membrane-proteins-captured-on-hiv-1-gag-virus-like-particles
#13
João Vidigal, Bárbara Fernandes, Mafalda M Dias, Marco Patrone, António Roldão, Manuel J T Carrondo, Paula M Alves, Ana P Teixeira
Conformationally complex membrane proteins (MPs) are therapeutic targets in many diseases, but drug discovery has been slowed down by the lack of efficient production tools. Co-expression of MPs with matrix proteins from enveloped viruses is a promising approach to obtain correctly folded proteins at the surface of virus-like particles (VLPs), preserving their native lipidic environment. Here, we implemented a site-specific recombinase-mediated cassette exchange (RMCE) strategy to establish a reusable HIV-1 Gag-expressing insect cell line for fast production of target MPs on the surface of Gag-VLPs...
November 16, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29143801/novel-molecular-challenges-in-targeting-anaplastic-lymphoma-kinase-in-alk-expressing-human-cancers
#14
REVIEW
Abdulraheem Alshareef
Targeting anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase receptor initially identified as a potent oncogenic driver in anaplastic large-cell lymphoma (ALCL) in the form of nucleophosmin (NPM)-ALK fusion protein, using tyrosine kinase inhibitors has shown to be a promising therapeutic approach for ALK-expressing tumors. However, clinical resistance to ALK inhibitors invariably occurs, and the molecular mechanisms are incompletely understood. Recent studies have clearly shown that clinical resistance to ALK inhibitors is a multifactorial and complex mechanism...
October 28, 2017: Cancers
https://www.readbyqxmd.com/read/29143083/the-polyphyletic-origins-of-primase-helicase-bifunctional-proteins
#15
Ankita Gupta, Supriya Patil, Ramya Vijayakumar, Kiran Kondabagil
We studied the evolutionary relationships of different primase-helicase bifunctional proteins, found mostly in viruses, virophages, plasmids, and organellar genomes, by phylogeny and correlation analysis. Our study suggests independent origins of primase-helicase bifunctional proteins resulting from multiple fusion events between genes encoding primase and helicase domains of different families. The correlation analysis further indicated strong functional dependencies of domains in the bifunctional proteins that are part of smaller genomes and plasmids...
November 15, 2017: Journal of Molecular Evolution
https://www.readbyqxmd.com/read/29142246/a-comprehensive-structural-biochemical-and-biological-profiling-of-the-human-nudix-hydrolase-family
#16
Jordi Carreras-Puigvert, Marinka Zitnik, Ann-Sofie Jemth, Megan Carter, Judith E Unterlass, Björn Hallström, Olga Loseva, Zhir Karem, José Manuel Calderón-Montaño, Cecilia Lindskog, Per-Henrik Edqvist, Damian J Matuszewski, Hammou Ait Blal, Ronnie P A Berntsson, Maria Häggblad, Ulf Martens, Matthew Studham, Bo Lundgren, Carolina Wählby, Erik L L Sonnhammer, Emma Lundberg, Pål Stenmark, Blaz Zupan, Thomas Helleday
The NUDIX enzymes are involved in cellular metabolism and homeostasis, as well as mRNA processing. Although highly conserved throughout all organisms, their biological roles and biochemical redundancies remain largely unclear. To address this, we globally resolve their individual properties and inter-relationships. We purify 18 of the human NUDIX proteins and screen 52 substrates, providing a substrate redundancy map. Using crystal structures, we generate sequence alignment analyses revealing four major structural classes...
November 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/29142129/entry-of-human-coronavirus-nl63-to-the-cell
#17
Aleksandra Milewska, Paulina Nowak, Katarzyna Owczarek, Artur Szczepanski, Miroslaw Zarebski, Agnieszka Hoang-Bujnowicz, Krzysztof Berniak, Jacek Wojarski, Slawomir Zeglen, Zbigniew Baster, Zenon Rajfur, Krzysztof Pyrc
First steps of human coronavirus NL63 (HCoV-NL63) infection were previously described. The virus binds to target cells by heparan sulfate proteoglycans, and interacts with the ACE2 protein. Subsequent events, including virus internalization and trafficking, remain to be elucidated. In this study, we mapped the process of HCoV-NL63 entry into LLC-Mk2 cell line and ex vivo 3D tracheobronchial tissue.Using a variety of techniques we have shown that HCoV-NL63 virions require endocytosis for successful entry to the LLC-MK2 cells, and interaction between the virus and the ACE2 molecule triggers recruitment of clathrin...
November 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29141910/munc13-proteins-control-regulated-exocytosis-in-mast-cells
#18
Elsa M Rodarte, Marco A Ramos, Alfredo J Davalos, Daniel C Moreira, David S Moreno, Eduardo I Cardenas, Alejandro I Rodarte, Youlia Petrova, Sofia Molina, Luis E Rendon, Elizabeth Sanchez, Keegan Breaux, Alejandro Tortoriello, John Manllo, Erika A Gonzalez, Michael J Tuvim, Burton F Dickey, Alan R Burns, Ruth Heidelberger, Roberto Adachi
Mast cells (MCs) are involved in host defenses against pathogen and inflammation. Stimulated MCs release substances stored in their granules via regulated exocytosis. In other cell types, Munc13 (mammalian homolog of C. elegans uncoordinated gene 13) proteins play essential roles in regulated exocytosis. Here, we found that MCs express Munc13-2 and -4, and studied their roles using global and conditional knockout (KO) mice. In a model of systemic anaphylaxis, we found no difference between WT and Munc13-2 KO mice, but global and MC-specific Munc13-4 KO mice developed less hypothermia...
November 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29141672/a-novel-git2-braf-fusion-in-pilocytic-astrocytoma
#19
Jeffrey Helgager, Hart G Lidov, Navin R Mahadevan, Mark W Kieran, Keith L Ligon, Sanda Alexandrescu
BACKGROUND: KIAA1549-BRAF fusion is the most common genetic event in pilocytic astrocytoma (PA), and leads to activation of the mitogen activated protein kinase (MAPK) signaling pathway. Fusions of BRAF with other partner genes, as well as other genetic alterations not involving BRAF but also leading to MAPK pathway activation have been described rarely. CASE PRESENTATION: We present a new fusion partner in the low-grade glioma of a 10-year-old male, who presented with headaches and recent episodes of seizures...
November 15, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/29141398/the-prognostic-significance-of-notch1-and-fatty-acid-binding-protein-7-fabp7-expression-in-resected-tracheobronchial-adenoid-cystic-carcinoma-a-multicenter-retrospective-study
#20
Mian Xie, Xiaojun Wu, Jinjun Zhang, Chaosheng He, Shenhai Wei, Junyao Huang, Xinge Fu, Yingying Gu
Purpose: Adenoid cystic carcinoma (ACC) of the trachea and bronchus is a rare tumor. Although MYB-NFIB oncogene fusion and Notch1 mutation have been identified in adenoid cystic carcinoma (ACC), little is known about the expression and clinical significance of Notch1 and its target gene fatty acid binding protein 7 (FABP7) in tracheobronchial ACC. Materials and Methods: Primary tracheobronchial ACC that were resected between 1998 and 2014 were identified through the pathology and oncology database from five thoracic oncology centers in China...
November 15, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
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