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ribosome inactivating protein

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https://www.readbyqxmd.com/read/28090686/effectively-enhancing-cytotoxic-and-apoptotic-effects-of-alpha-momorcharin-by-integrating-a-heparin-binding-peptide
#1
Meng-Jie Tan, Xue-Wei Cao, Peng-Fei Li, Yi-Zhou Zhai, Yu Zhou, Ye-Jun Liu, Jian Zhao, Fu-Jun Wang
Alpha-momorcharin (α-MMC), a type I ribosome inactivating protein, has attracted a great deal attention because of its antitumor activity. However, the cytotoxicity of α-MMC is limited due to insufficient cellular internalization in cancer cells. To enhance the cytotoxicity of α-MMC, a heparin-binding domain derived from HB-EGF (named HBP) was used as a cell-penetrating peptide and fused to the C-terminus of α-MMC. This novel α-MMC-HBP fusion protein was expressed and purified with a Ni(2+) -resin. The N-glycosidase activity and DNase activity assay indicated that the introduction of HBP did not interfere with the intrinsic bioactivities of α-MMC...
January 16, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28088476/a-chimeric-protein-of-abrin-and-abrus-precatorius-agglutinin-that-neutralizes-abrin-mediated-lethality-in-mice
#2
Vinita Tiwari, Shradha Bagaria, Anjali A Karande
Abrin, a type II ribosome inactivating protein from the Abrus precatorius plant, is extremely toxic. It has been shown to be 75 times more potent than its infamous sister toxin, ricin and their potential use in bio-warfare is a cause of major concern. Although several vaccine candidates are under clinical trials for ricin, none are available against abrin. The present study proposes a chimeric protein, comprising of 1-123 amino acids taken from the A chain of abrin and 124-175 amino acids from Abrus precatorius agglutinin A chain, as a vaccine candidate against abrin intoxication...
January 11, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28067841/lectin-digestibility-and-stability-of-elderberry-antioxidants-to-heat-treatment-in-vitro
#3
Pilar Jiménez, Patricia Cabrero, Damian Cordoba-Diaz, Manuel Cordoba-Diaz, Manuel Garrosa, Tomás Girbés
Elderberry contains healthy low molecular weight nutraceuticals and lectins which are sequence-related to the elderberry allergen Sam n1. Some of these lectins are type II ribosome-inactivating proteins. The sensitivity of native lectins present in elderberry fruits and bark to the proteolysis triggered by in vitro simulated gastric and duodenal fluids has been investigated. It was found that these lectins are refractory to proteolysis. Nonetheless, incubation for 5-10 min in a boiling water bath completely sensitized them to the hydrolytic enzymes in vitro...
January 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28029105/cathepsin-b-degradable-nir-responsive-nanoparticulate-platform-for-target-specific-cancer-therapy
#4
Sam P Tarassoli, Alejandra Martinez de Pinillos Bayona, Hayley Pye, C Alexander Mosse, John F Callan, Alexander MacRobert, Anthony P McHale, Nikolitsa Nomikou
Stimuli-responsive anticancer formulations can promote drug release and activation within the target tumour, facilitate cellular uptake, as well as improve the therapeutic efficacy of drugs and reduce off-target effects. In the present work, indocyanine green (ICG)-containing polyglutamate (PGA) nanoparticles were developed and characterized. Digestion of nanoparticles with cathepsin B, a matrix metalloproteinase overexpressed in the microenvironment of advanced tumours, decreased particle size and increased ICG cellular uptake...
February 3, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28028039/draft-genome-sequence-of-bitter-gourd-momordica-charantia-a-vegetable-and-medicinal-plant-in-tropical-and-subtropical-regions
#5
Naoya Urasaki, Hiroki Takagi, Satoshi Natsume, Aiko Uemura, Naoki Taniai, Norimichi Miyagi, Mai Fukushima, Shouta Suzuki, Kazuhiko Tarora, Moritoshi Tamaki, Moriaki Sakamoto, Ryohei Terauchi, Hideo Matsumura
Bitter gourd (Momordica charantia) is an important vegetable and medicinal plant in tropical and subtropical regions globally. In this study, the draft genome sequence of a monoecious bitter gourd inbred line, OHB3-1, was analyzed. Through Illumina sequencing and de novo assembly, scaffolds of 285.5 Mb in length were generated, corresponding to ∼84% of the estimated genome size of bitter gourd (339 Mb). In this draft genome sequence, 45,859 protein-coding gene loci were identified, and transposable elements accounted for 15...
December 27, 2016: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28009354/rsk-mediated-nuclear-accumulation-of-the-cold-shock-y-box-protein-1-controls-proliferation-of-t-cells-and-t-all-blasts
#6
Steffi Gieseler-Halbach, Stefan Meltendorf, Mandy Pierau, Soenke Weinert, Florian H Heidel, Thomas Fischer, Juliane Handschuh, Ruediger C Braun-Dullaeus, Martin Schrappe, Jonathan A Lindquist, Peter R Mertens, Ulrich Thomas, Monika C Brunner-Weinzierl
Deregulated proliferation is key to tumor progression. Although unrestricted proliferation of solid tumor cells correlates with the cold-shock protein Y-box (YB)-binding protein-1 accumulation in the nuclei, little is known about its expression and function in hematopoietic malignancies, such as T-cell acute lymphoblastic leukemia (T-ALL). Here we show that YB-1 protein is highly enriched in the nuclei of activated T cells and malignant human T-ALL cell lines but not in resting T cells. YB-1 S(102) mutations that either mimic (S102D) or prevent phosphorylation (S102N) led to accumulation of YB-1 in the nucleus of T cells or strictly excluded it, respectively...
December 23, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28003804/golden-needle-mushroom-a-culinary-medicine-with-evidenced-based-biological-activities-and-health-promoting-properties
#7
REVIEW
Calyn Tang, Pearl Ching-Xin Hoo, Loh Teng-Hern Tan, Priyia Pusparajah, Tahir Mehmood Khan, Learn-Han Lee, Bey-Hing Goh, Kok-Gan Chan
Flammulina velutipes (enoki, velvet shank, golden needle mushroom or winter mushroom), one of the main edible mushrooms on the market, has long been recognized for its nutritional value and delicious taste. In recent decades, research has expanded beyond detailing its nutritional composition and delved into the biological activities and potential health benefits of its constituents. Many bioactive constituents from a range of families have been isolated from different parts of the mushroom, including carbohydrates, protein, lipids, glycoproteins, phenols, and sesquiterpenes...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27999336/debouganin-diabody-fusion-protein-overcomes-drug-resistance-to-adcs-comprised-of-anti-microtubule-agents
#8
Shilpa Chooniedass, Rachelle L Dillon, Arjune Premsukh, Peter J Hudson, Gregory P Adams, Glen C MacDonald, Jeannick Cizeau
Antibody drug conjugates (ADC), comprised of highly potent small molecule payloads chemically conjugated to a full-length antibody, represent a growing class of therapeutic agents. The targeting of cytotoxic payloads via the specificity and selectivity of the antibody has led to substantial clinical benefits. However, ADC potency can be altered by mechanisms of resistance such as overexpression of efflux pumps or anti-apoptotic proteins. DeBouganin is a de-immunized variant of bouganin, a ribosome-inactivating protein (RIP) that blocks protein synthesis, thereby leading to apoptosis...
December 17, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27993682/trastuzumab-stimulation-of-ribosomal-protein-s6-kinase-1-s6k1-predicts-de-novo-trastuzumab-resistance
#9
Felicia C Huynh, Daniel Nguyen, Frank E Jones
Breast cancer is a complex disease with at least five different molecular subtypes identified. The breast tumor molecular subtypes guide stratification of patients for specific targeted therapy regimens and each subtype is associated with significantly different patient outcomes. For example, patients with the HER2 positive molecular subtype benefit from the HER2 targeted therapy trastuzumab. Unfortunately, women with the HER2 positive molecular subtype have the worst overall prognosis and nearly 70% of women with HER2 positive breast cancer exhibit de novo or acquired resistance to trastuzumab...
December 18, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27959964/proteomic-analysis-of-eif5b-silencing-modulated-proteostasis
#10
Xu Jiang, Xiaoyong Jiang, Yun Feng, Renhua Xu, Qingtao Wang, Haiteng Deng
Protein translational machinery is an important component of the proteostasis network that maintains cellular proteostasis and regulates aging and other cellular processes. Ample evidence indicates that inhibition of translation initiation factor activities enhances stress resistance in model organisms. Eukaryotic translation initiation factor 5B (eIF5B) acts by joining the pre-40S subunit with the 60S ribosomal unit to form an 80S-like complex during protein translational initiation. Reduced eIF5B expression may disrupt proteostasis and trigger cellular processes associated with stress responses...
2016: PloS One
https://www.readbyqxmd.com/read/27956701/the-chromatin-associated-phf12-protein-maintains-nucleolar-integrity-and-prevents-premature-cellular-senescence
#11
Richard Graveline, Katarzyna Marcinkiewicz, Seyun Choi, Marilène Paquet, Wolfgang Wurst, Thomas Floss, Gregory David
PF1, also known as PHF12 (plant homeodomain (PHD) zinc finger protein 12) is a member of the PHD zinc finger family of proteins. PF1 associates with a chromatin interacting protein complex comprised of MRG15, Sin3B, and HDAC1, that functions as a transcriptional modulator. The biological function of Pf1 remains largely elusive. We undertook the generation of Pf1 knockout mice to elucidate its physiological role. We demonstrate that Pf1 is required for mid-to-late gestation viability. Pf1 inactivation impairs the proliferative potential of the mouse embryonic fibroblasts (MEFs), and is associated with a significant decrease in BrdU incorporation, an increase in SA-β-gal activity, a marker of cellular senescence and elevated levels of phosphorylated H2AX (γ-H2AX), a marker associated with DNA double-strand breaks...
December 12, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27939605/dynamics-of-the-escherichia-coli-proteome-in-response-to-nitrogen-starvation-and-entry-into-the-stationary-phase
#12
Heloisa B S Sanchuki, Fernanda Gravina, Thiago E Rodrigues, Edileusa C M Gerhardt, Fábio O Pedrosa, Emanuel M Souza, Roberto T Raittz, Glaucio Valdameri, Gustavo A de Souza, Luciano F Huergo
Nitrogen is needed for the biosynthesis of biomolecules including proteins and nucleic acids. In the absence of fixed nitrogen prokaryotes such as E. coli immediately ceases growth. Ammonium is the preferred nitrogen source for E. coli supporting the fastest growth rates. Under conditions of ammonium limitation, E. coli can use alternative nitrogen sources to supply ammonium ions and this reprogramming is led by the induction of the NtrC regulon. Here we used label free proteomics to determine the dynamics of E...
December 8, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27933947/in-silico-discovery-and-validation-of-amide-based-small-molecule-targeting-the-enzymatic-site-of-shiga-toxin
#13
Vinita Chauhan, Dilip Chaudhary, Uma Pathak, Nandita Saxena, Ram Kumar Dhaked
Shiga toxin (Stx), a category B biothreat agent, is a ribosome inactivating protein and toxic to human and animals. Here, we designed and synthesized small molecules that block the active site of the Stx A subunit. On the basis of binding energy, 20 molecules were selected for synthesis and evaluation. These molecules were primarily screened using fluorescence-based thermal shift assay and in vitro in Vero cells. Among 32 molecules (including 12 reported), six molecules offered protection with IC50 of 2.60-23...
December 8, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27929418/yeast-reporter-assay-to-identify-cellular-components-of-ricin-toxin-a-chain-trafficking
#14
Björn Becker, Tina Schnöder, Manfred J Schmitt
RTA, the catalytic A-subunit of the ribosome inactivating A/B toxin ricin, inhibits eukaryotic protein biosynthesis by depurination of 28S rRNA. Although cell surface binding of ricin holotoxin is mainly mediated through its B-subunit (RTB), sole application of RTA is also toxic, albeit to a significantly lower extent, suggesting alternative pathways for toxin uptake and transport. Since ricin toxin trafficking in mammalian cells is still not fully understood, we developed a GFP-based reporter assay in yeast that allows rapid identification of cellular components required for RTA uptake and subsequent transport through a target cell...
December 6, 2016: Toxins
https://www.readbyqxmd.com/read/27903650/structural-analysis-of-single-domain-antibodies-bound-to-a-second-neutralizing-hot-spot-on-ricin-toxin-s-enzymatic-subunit
#15
Michael J Rudolph, David J Vance, Michael S Cassidy, Yinghui Rong, Nicholas J Mantis
Ricin toxin is a heterodimer consisting of RTA, a ribosome-inactivating protein, and RTB, a lectin that facilitates receptor-mediated uptake into mammalian cells. In previous studies, we demonstrated that toxin-neutralizing antibodies target four spatially distinct hotspots on RTA, which we refer to as epitope Clusters I-IV. In this report we identified and characterized three single domain camelid antibodies (VHH) against Cluster II. One of these VHHs, V5E1, ranks as one of the most potent ricin-neutralizing antibodies described to date...
November 30, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27898041/ribosome-inactivating-proteins-from-plants-a-historical-overview
#16
REVIEW
Andrea Bolognesi, Massimo Bortolotti, Stefania Maiello, Maria Giulia Battelli, Letizia Polito
This review provides a historical overview of the research on plant ribosome-inactivating proteins (RIPs), starting from the first studies at the end of eighteenth century involving the purification of abrin and ricin, as well as the immunological experiments of Paul Erlich. Interest in these plant toxins was revived in 1970 by the observation of their anticancer activity, which has given rise to a large amount of research contributing to the development of various scientific fields. Biochemistry analyses succeeded in identifying the enzymatic activity of RIPs and allowed for a better understanding of the ribosomal machinery...
November 26, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27892500/four-translation-initiation-pathways-employed-by-the-leaderless-mrna-in-eukaryotes
#17
Kseniya A Akulich, Dmitry E Andreev, Ilya M Terenin, Victoria V Smirnova, Aleksandra S Anisimova, Desislava S Makeeva, Valentina I Arkhipova, Elena A Stolboushkina, Maria B Garber, Maria M Prokofjeva, Pavel V Spirin, Vladimir S Prassolov, Ivan N Shatsky, Sergey E Dmitriev
mRNAs lacking 5' untranslated regions (leaderless mRNAs) are molecular relics of an ancient translation initiation pathway. Nevertheless, they still represent a significant portion of transcriptome in some taxons, including a number of eukaryotic species. In bacteria and archaea, the leaderless mRNAs can bind non-dissociated 70 S ribosomes and initiate translation without protein initiation factors involved. Here we use the Fleeting mRNA Transfection technique (FLERT) to show that translation of a leaderless reporter mRNA is resistant to conditions when eIF2 and eIF4F, two key eukaryotic translation initiation factors, are inactivated in mammalian cells...
November 28, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27886256/structural-insights-into-the-interaction-of-the-ribosomal-p-stalk-protein-p2-with-a-type-ii-ribosome-inactivating-protein-ricin
#18
Xiaojiao Fan, Yuwei Zhu, Chongyuan Wang, Liwen Niu, Maikun Teng, Xu Li
Ricin is a type II ribosome-inactivating protein (RIP) that depurinates A(4324) at the sarcin-ricin loop of 28 S ribosomal RNA (rRNA), thus inactivating the ribosome by preventing elongation factors from binding to the GTPase activation centre. Recent studies have disclosed that the conserved C-terminal domain (CTD) of eukaryotic ribosomal P stalk proteins is involved in the process that RIPs target ribosome. However, the details of the molecular interaction between ricin and P stalk proteins remain unknown...
November 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27881976/the-roles-of-alpha-momorcharin-and-jasmonic-acid-in-modulating-the-response-of-momordica-charantia-to-cucumber-mosaic-virus
#19
Ting Yang, Yao Meng, Li-Juan Chen, Hong-Hui Lin, De-Hui Xi
Alpha-momorcharin (α-MMC) is a type-I ribosome inactivating protein with a molecular weight of 29 kDa that is found in Momordica charantia, and has been shown to be effective against a broad range of human viruses as well as having anti-tumor activities. However, the role of endogenous α-MMC under viral infection and the mechanism of the anti-viral activities of α-MMC in plants are still unknown. To study the effect of α-MMC on plant viral defense and how α-MMC increases plant resistance to virus, the M...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27879643/structures-and-ribosomal-interaction-of-ribosome-inactivating-proteins
#20
REVIEW
Wei-Wei Shi, Amanda Nga-Sze Mak, Kam-Bo Wong, Pang-Chui Shaw
Ribosome-inactivating proteins (RIPs) including ricin, Shiga toxin, and trichosanthin, are RNA N-glycosidases that depurinate a specific adenine residue (A-4324 in rat 28S ribosomal RNA, rRNA) in the conserved α-sarcin/ricin loop (α-SRL) of rRNA. RIPs are grouped into three types according to the number of subunits and the organization of the precursor sequences. RIPs are two-domain proteins, with the active site located in the cleft between the N- and C-terminal domains. It has been found that the basic surface residues of the RIPs promote rapid and specific targeting to the ribosome and a number of RIPs have been shown to interact with the C-terminal regions of the P proteins of the ribosome...
November 21, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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