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https://www.readbyqxmd.com/read/27899666/structures-of-human-srp72-complexes-provide-insights-into-srp-rna-remodeling-and-ribosome-interaction
#1
Matthias M M Becker, Karine Lapouge, Bernd Segnitz, Klemens Wild, Irmgard Sinning
Co-translational protein targeting and membrane protein insertion is a fundamental process and depends on the signal recognition particle (SRP). In mammals, SRP is composed of the SRP RNA crucial for SRP assembly and function and six proteins. The two largest proteins SRP68 and SRP72 form a heterodimer and bind to a regulatory site of the SRP RNA. Despite their essential roles in the SRP pathway, structural information has been available only for the SRP68 RNA-binding domain (RBD). Here we present the crystal structures of the SRP68 protein-binding domain (PBD) in complex with SRP72-PBD and of the SRP72-RBD bound to the SRP S domain (SRP RNA, SRP19 and SRP68) detailing all interactions of SRP72 within SRP...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27819178/myelodysplastic-syndromes-and-acute-leukemia-with-genetic-predispositions-a-new-challenge-for-hematologists
#2
Nicolas Duployez, Sophie Lejeune, Aline Renneville, Claude Preudhomme
The determination of an underlying genetic predisposition is not automatically part of the diagnosis of hematological malignancies (HM) in routine practice. However, it is assumed that genetic predispositions to HM are currently underestimated due to great variations in disease phenotype, variable latency and incomplete penetrance. Most of patients do not display any biological or clinical signs besides the overt hematological disease and many of them have a lack of personal or family history of malignancies...
December 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27384852/genetic-predisposition-to-pediatric-myeloid-malignancies
#3
Hideki Muramatsu
Various genetic disorders are known to be associated with cancer predisposition. For example, children with Down syndrome are predisposed to developing acute myeloid leukemia, and those with RASopathies, such as Noonan syndrome, are predisposed to juvenile myelomonocytic leukemia. To date, more than 250 diseases or syndromes have been reported to be associated with the development of pediatric cancers. Recently, the advent of the massive parallel sequencing technique revealed several germline mutations, including RUNX1, CEBPA, GATA2, SRP72, ETV6, and DDX41, which are associated with familial myeloid malignancies...
June 2016: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/27248996/hereditary-predispositions-to-myelodysplastic-syndrome
#4
REVIEW
Sarah A Bannon, Courtney D DiNardo
Myelodysplastic syndromes (MDS) are heterogeneous clonal hematopoietic disorders characterized by ineffective hematopoiesis, bone marrow dysplasia, and peripheral cytopenias. Familial forms of MDS have traditionally been considered rare, especially in adults; however, the increasing availability of somatic and germline genetic analyses has identified multiple susceptibility loci. Bone marrow failure syndromes have been well-described in the pediatric setting, e.g., Fanconi anemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anemia (DBA), and Shwachman-Diamond syndrome (SBS), hallmarked by clinically-recognizable phenotypes (e...
May 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/26881866/classification-of-cholestatic-and-necrotic-hepatotoxicants-using-transcriptomics-on-human-precision-cut-liver-slices
#5
Suresh Vatakuti, Jeroen L A Pennings, Emilia Gore, Peter Olinga, Geny M M Groothuis
Human toxicity screening is an important stage in the development of safe drug candidates. Hepatotoxicity is one of the major reasons for the withdrawal of drugs from the market because the liver is the major organ involved in drug metabolism, and it can generate toxic metabolites. There is a need to screen molecules for drug-induced hepatotoxicity in humans at an earlier stage. Transcriptomics is a technique widely used to screen molecules for toxicity and to unravel toxicity mechanisms. To date, the majority of such studies were performed using animals or animal cells, with concomitant difficulty in interpretation due to species differences, or in human hepatoma cell lines or cultured hepatocytes, suffering from the lack of physiological expression of enzymes and transporters and lack of nonparenchymal cells...
March 21, 2016: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/26876264/-clinical-and-genetic-background-of-familial-myelodysplasia-and-acute-myeloid-leukemia
#6
REVIEW
Péter Attila Király, Krisztián Kállay, Dóra Marosvári, Gábor Benyó, Anita Szőke, Judit Csomor, Csaba Bödör
Myelodysplastic syndrome and acute myeloid leukaemia are mainly sporadic diseases, however, rare familial cases exist. These disorders are considered rare, but are likely to be more common than currently appreciated, and are characterized by the autosomal dominant mutations of hematopoietic transcription factors. These syndromes have typical phenotypic features and are associated with an increased risk for developing overt malignancy. Currently, four recognized syndromes could be separated: familial acute myeloid leukemia with mutated CEBPA, familial myelodysplastic syndrome/acute myeloid leukemia with mutated GATA2, familial platelet disorder with propensity to myeloid malignancy with RUNX1 mutations, and telomere biology disorders due to mutations of TERC or TERT...
February 21, 2016: Orvosi Hetilap
https://www.readbyqxmd.com/read/26561982/signal-recognition-particle-immunoglobulin-g-detected-incidentally-associates-with-autoimmune-myopathy
#7
Metha Apiwattanakul, Margherita Milone, Sean J Pittock, Thomas J Kryzer, James P Fryer, Orna O'toole, Andrew Mckeon, Vanda A Lennon
INTRODUCTION: Paraneoplastic autoantibody screening of 150,000 patient sera by tissue-based immunofluorescence incidentally revealed 170 with unsuspected signal recognition particle (SRP) immunoglobulin G (IgG), which is a recognized biomarker of autoimmune myopathy. Of the 77 patients with available information, 54 had myopathy. We describe the clinical/laboratory associations. METHODS: Distinctive cytoplasm-binding IgG (mouse tissue substrate) prompted western blot, enzyme-linked immunoassay, and immunoprecipitation analyses...
June 2016: Muscle & Nerve
https://www.readbyqxmd.com/read/25659730/genetic-predisposition-syndromes-when-should-they-be-considered-in-the-work-up-of-mds
#8
REVIEW
Daria V Babushok, Monica Bessler
Myelodysplastic syndromes (MDS) are clonal hematopoietic disorders characterized by cytopenias, ineffective hematopoiesis, myelodysplasia, and an increased risk of acute myeloid leukemia (AML). While sporadic MDS is primarily a disease of the elderly, MDS in children and young and middle-aged adults is frequently associated with underlying genetic predisposition syndromes. In addition to the classic hereditary bone marrow failure syndromes (BMFS) such as Fanconi Anemia and Dyskeratosis Congenita, in recent years there has been an increased awareness of non-syndromic familial MDS/AML predisposition syndromes such as those caused by mutations in GATA2, RUNX1, CEBPA, and SRP72 genes...
March 2015: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/24700861/srp-rna-remodeling-by-srp68-explains-its-role-in-protein-translocation
#9
Jan Timo Grotwinkel, Klemens Wild, Bernd Segnitz, Irmgard Sinning
The signal recognition particle (SRP) is central to membrane protein targeting; SRP RNA is essential for SRP assembly, elongation arrest, and activation of SRP guanosine triphosphatases. In eukaryotes, SRP function relies on the SRP68-SRP72 heterodimer. We present the crystal structures of the RNA-binding domain of SRP68 (SRP68-RBD) alone and in complex with SRP RNA and SRP19. SRP68-RBD is a tetratricopeptide-like module that binds to a RNA three-way junction, bends the RNA, and inserts an α-helical arginine-rich motif (ARM) into the major groove...
April 4, 2014: Science
https://www.readbyqxmd.com/read/24434517/plasmodium-falciparum-signal-recognition-particle-components-and-anti-parasitic-effect-of-ivermectin-in-blocking-nucleo-cytoplasmic-shuttling-of-srp
#10
M Panchal, K Rawat, G Kumar, K M Kibria, S Singh, Md Kalamuddin, A Mohmmed, P Malhotra, R Tuteja
Signal recognition particle (SRP) is a ubiquitous ribonucleoprotein complex that targets proteins to endoplasmic reticulum (ER) in eukaryotes. Here we report that Plasmodium falciparum SRP is composed of six polypeptides; SRP9, SRP14, SRP19, SRP54, SRP68 and SRP72 and a 303nt long SRP RNA. We generated four transgenic parasite lines expressing SRP-GFP chimeric proteins and co-localization studies showed the nucleo-cytoplasmic localization for these proteins. The evaluation of the effect of known SRP and nuclear import/export inhibitors on P...
2014: Cell Death & Disease
https://www.readbyqxmd.com/read/23437149/profiling-of-rna-degradation-for-estimation-of-post-mortem-corrected-interval
#11
Fernanda Sampaio-Silva, Teresa Magalhães, Félix Carvalho, Ricardo Jorge Dinis-Oliveira, Ricardo Silvestre
An estimation of the post mortem interval (PMI) is frequently touted as the Holy Grail of forensic pathology. During the first hours after death, PMI estimation is dependent on the rate of physical observable modifications including algor, rigor and livor mortis. However, these assessment methods are still largely unreliable and inaccurate. Alternatively, RNA has been put forward as a valuable tool in forensic pathology, namely to identify body fluids, estimate the age of biological stains and to study the mechanism of death...
2013: PloS One
https://www.readbyqxmd.com/read/23048028/a-novel-histone-h4-arginine-3-methylation-sensitive-histone-h4-binding-activity-and-transcriptional-regulatory-function-for-signal-recognition-particle-subunits-srp68-and-srp72
#12
Jingjing Li, Fan Zhou, Deguo Zhan, Qinqin Gao, Nan Cui, Jiwen Li, Elena Iakhiaeva, Christian Zwieb, Biaoyang Lin, Jiemin Wong
BACKGROUND: Histone methylation is believed to recruit specific histone-binding proteins. RESULTS: We identified SRP68/72 heterodimers as major nuclear proteins whose binding of histone H4 tail is inhibited by H4R3 methylation. CONCLUSION: SRP68/72 are novel histone H4-binding proteins. SIGNIFICANCE: Uncovers a novel chromatin regulatory function for SRP68/72 and suggests that histone arginine methylation may function mainly in inhibiting rather than recruiting effector proteins...
November 23, 2012: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/22541560/exome-sequencing-identifies-autosomal-dominant-srp72-mutations-associated-with-familial-aplasia-and-myelodysplasia
#13
Michael Kirwan, Amanda J Walne, Vincent Plagnol, Mark Velangi, Aloysius Ho, Upal Hossain, Tom Vulliamy, Inderjeet Dokal
Aplastic anemia (AA) and myelodysplasia (MDS) are forms of bone marrow failure that are often part of the same progressive underlying disorder. While most cases are simplex and idiopathic, some show a clear pattern of inheritance; therefore, elucidating the underlying genetic cause could lead to a greater understanding of this spectrum of disorders. We used a combination of exome sequencing and SNP haplotype analysis to identify causative mutations in a family with a history of autosomal-dominant AA/MDS. We identified a heterozygous mutation in SRP72, a component of the signal recognition particle (SRP) that is responsible for the translocation of nascent membrane-bound and excreted proteins to the endoplasmic reticulum...
May 4, 2012: American Journal of Human Genetics
https://www.readbyqxmd.com/read/21794664/-histological-and-molecular-alterations-in-inflammatory-myopathies
#14
Mónica Vázquez Del Mercado Espinosa, Víctor Arana Argaez, Marcelo Heron Petri, Jorge Aguilar Arreola
The histological findings in muscle biopsies of inflammatory myopathies have been divided into 2 groups: A) Endomisial infiltrates mainly by T CD8+, CD4+ and macrophages and B) Perivascular infiltrates by CD4+, B cells and macrophages. The first kind of infiltrate suggests an immune reaction against muscle fibers very common in PM and inclusion body myositis, On the other hand the perivascular infiltrate is a hallmark of DM. It has ben shown that autoantigens related with myopathies such as Mi-2, Jo-1, OJ, PL12, Ku, PM/Scl are able to suffer proteolytic cleavage by granzyme B and other stimulus induced by cytotoxic T cells...
November 2009: Reumatología Clinica
https://www.readbyqxmd.com/read/21734034/ribosomal-protein-s6-interacts-with-the-latency-associated-nuclear-antigen-of-kaposi-s-sarcoma-associated-herpesvirus
#15
Wuguo Chen, Dirk P Dittmer
The latency-associated nuclear antigen (LANA) is central to the maintenance of Kaposi's sarcoma-associated herpesvirus (KSHV) and to the survival of KSHV-carrying tumor cells. In an effort to identify interaction partners of LANA, we purified authentic high-molecular-weight complexes of LANA by conventional chromatography followed by immunoprecipitation from the BC-3 cell line. This is the first analysis of LANA-interacting partners that is not based on forced ectopic expression of LANA. Subsequent tandem mass spectrometry (MS/MS) analysis identified many of the known LANA-interacting proteins...
September 2011: Journal of Virology
https://www.readbyqxmd.com/read/21073748/identification-of-amino-acid-residues-in-protein-srp72-required-for-binding-to-a-kinked-5e-motif-of-the-human-signal-recognition-particle-rna
#16
Elena Iakhiaeva, Alexei Iakhiaev, Christian Zwieb
BACKGROUND: Human cells depend critically on the signal recognition particle (SRP) for the sorting and delivery of their proteins. The SRP is a ribonucleoprotein complex which binds to signal sequences of secretory polypeptides as they emerge from the ribosome. Among the six proteins of the eukaryotic SRP, the largest protein, SRP72, is essential for protein targeting and possesses a poorly characterized RNA binding domain. RESULTS: We delineated the minimal region of SRP72 capable of forming a stable complex with an SRP RNA fragment...
2010: BMC Molecular Biology
https://www.readbyqxmd.com/read/20729213/inhibitors-of-mapk-pathway-erk1-2-or-p38-prevent-the-il-1-beta-induced-up-regulation-of-srp72-autoantigen-in-jurkat-cells
#17
Victor E Arana-Argáez, Vidal Delgado-Rizo, Oscar E Pizano-Martínez, Erika A Martínez-Garcia, Beatriz T Martín-Márquez, Andrea Muñoz-Gómez, Marcelo H Petri, Juan Armendáriz-Borunda, Guillermo Espinosa-Ramírez, Diego A Zúñiga-Tamayo, Rafael Herrera-Esparza, Mónica Vázquez-Del Mercado
Phosphorylation is the most important post-translational event at a cellular level that is regulated by protein kinases. MAPK is a key player in the important cellular signaling pathway. It has been hypothesized that phosphorylation might have a role in the induction of break tolerance against some autoantigens such as SRP72. The aim of this study was to explore the pathways of phosphorylation and overexpression of the SRP72 polypeptide, using an in vitro model of Jurkat cells stimulated by recombinant human (rh)IL-1β in the presence of MAPK inhibitors...
October 22, 2010: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/20672053/archaea-signal-recognition-particle-shows-the-way
#18
REVIEW
Christian Zwieb, Shakhawat Bhuiyan
Archaea SRP is composed of an SRP RNA molecule and two bound proteins named SRP19 and SRP54. Regulated by the binding and hydrolysis of guanosine triphosphates, the RNA-bound SRP54 protein transiently associates not only with the hydrophobic signal sequence as it emerges from the ribosomal exit tunnel, but also interacts with the membrane-associated SRP receptor (FtsY). Comparative analyses of the archaea genomes and their SRP component sequences, combined with structural and biochemical data, support a prominent role of the SRP RNA in the assembly and function of the archaea SRP...
2010: Archaea: An International Microbiological Journal
https://www.readbyqxmd.com/read/19693936/characterization-of-the-srp68-72-interface-of-human-signal-recognition-particle-by-systematic-site-directed-mutagenesis
#19
Elena Iakhiaeva, Cynthia S Hinck, Andrew P Hinck, Christian Zwieb
The signal recognition particle (SRP) is a ribonucleoprotein complex which is crucial for the delivery of proteins to cellular membranes. Among the six proteins of the eukaryotic SRP, the two largest, SRP68 and SRP72, form a stable SRP68/72 heterodimer of unknown structure which is required for SRP function. Fragments 68e' (residues 530 to 620) and 72b' (residues 1 to 166) participate in the SRP68/72 interface. Both polypeptides were expressed in Escherichia coli and assembled into a complex which was stable at high ionic strength...
October 2009: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/18663994/identification-of-differentially-expressed-genes-in-4-day-axolotl-limb-blastema-by-suppression-subtractive-hybridization
#20
M Gorsic, G Majdic, R Komel
The goal of our study was the identification of up-regulated genes during axolotl (Ambystoma mexicanum) hindlimb regeneration 4 days after amputation using suppression subtractive hybridization (SSH). Approximately 400 clones that harbored upregulated genes in regenerating blastema tissue were selected for sequence analysis. A BLAST homology search against NCBI non-redundant database and an ambystoma EST database revealed 102 clones that showed homology to known sequences in GenBank with annotated function, 31 were known genes without known function, 74 were novel and 72 belonged to mitochondrial sequences...
March 2008: Journal of Physiology and Biochemistry
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