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ribosome inactivating protein

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https://www.readbyqxmd.com/read/28701787/avian-reovirus-p17-and-%C3%AF-a-act-cooperatively-to-downregulate-akt-by-suppressing-mtorc2-and-cdk2-cyclin-a2-and-upregulating-proteasome-psmb6
#1
Wei-Ru Huang, Pei-I Chi, Hung-Chuan Chiu, Jue-Liang Hsu, Brent L Nielsen, Tsai-Ling Liao, Hung-Jen Liu
Although we have shown that avian reovirus (ARV) p17-mediated inhibition of Akt leads to induction of autophagy, the precise mechanisms remain largely unknown. This study has identified a specific mechanism by which ARV coordinately regulates the degradation of ribosomal proteins by p17-mediated activation of E3 ligase MDM2 that targets ribosomal proteins and by σA-mediated upregulation of proteasome PSMB6. In addition to downregulating ribosomal proteins, p17 reduces mTORC2 assembly and disrupts mTORC2-robosome association, both of which inactivate mTORC2 leading to inhibition of Akt phosphorylation at S473...
July 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28693237/inhibitory-effects-of-delphinidin-on-the-proliferation-of-ovarian-cancer-cells-via-pi3k-akt-and-erk-1-2-mapk-signal-transduction
#2
Whasun Lim, Gwonhwa Song
Delphinidin is a member of the anthocyanidin family and is a natural pigment in red cabbage, berries, sweet potatoes and grapes. It possesses nutraceutical properties against various chronic diseases and types of cancer. However, little is known about its preventative effects on epithelial ovarian cancer, a disease that is associated with a low survival rate, a poor prognosis and a high rate of recurrence. The results of the present study demonstrated that the proliferation of SKOV3 cells decreased in a dose-dependent manner in response to treatment with delphinidin, and the phosphorylation of carcinogenic protein kinases associated with the progression of epithelial ovarian cancer was affected by delphinidin treatment...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28683136/generality-of-toxins-in-defensive-symbiosis-ribosome-inactivating-proteins-and-defense-against-parasitic-wasps-in-drosophila
#3
Matthew J Ballinger, Steve J Perlman
While it has become increasingly clear that multicellular organisms often harbor microbial symbionts that protect their hosts against natural enemies, the mechanistic underpinnings underlying most defensive symbioses are largely unknown. Spiroplasma bacteria are widespread associates of terrestrial arthropods, and include strains that protect diverse Drosophila flies against parasitic wasps and nematodes. Recent work implicated a ribosome-inactivating protein (RIP) encoded by Spiroplasma, and related to Shiga-like toxins in enterohemorrhagic Escherichia coli, in defense against a virulent parasitic nematode in the woodland fly, Drosophila neotestacea...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28680592/hif-prolyl-hydroxylase-phd3-regulates-translational-machinery-and-glucose-metabolism-in-clear-cell-renal-cell-carcinoma
#4
Petra Miikkulainen, Heidi Högel, Krista Rantanen, Tomi Suomi, Petri Kouvonen, Laura L Elo, Panu M Jaakkola
BACKGROUND: A key feature of clear cell renal cell carcinoma (ccRCC) is the inactivation of the von Hippel-Lindau tumour suppressor protein (pVHL) that leads to the activation of hypoxia-inducible factor (HIF) pathway also in well-oxygenated conditions. Important regulator of HIF-α, prolyl hydroxylase PHD3, is expressed in high amounts in ccRCC. Although several functions and downstream targets for PHD3 in cancer have been suggested, the role of elevated PHD3 expression in ccRCC is not clear...
2017: Cancer & Metabolism
https://www.readbyqxmd.com/read/28664270/curcin-c-a-novel-type-i-ribosome-inactivating-protein-from-the-post-germinating-cotyledons-of-jatropha-curcas
#5
Yangxue Zhang, Qian Yang, Chenyang Li, Mengmeng Ding, Xueyan Lv, Chengqiu Tao, Hongwu Yu, Fang Chen, Ying Xu
A novel type I ribosome-inactivating protein (RIP), designated as curcin C, was purified from Jatropha curcas, an important feedback source of bio-fuel. Molecular mass and isoelectric point of curcin C were 31.398 kDa and 7.12 as detected by MALTI-TOF assay and capillary electrophoresis assay, respectively. N-terminal sequence and LC-MS/MS analyses confirmed that curcin C is a type I RIP having high homology, but not the exactly the same with curcin, another type 1 RIP isolated from the endosperm of J. curcas...
June 29, 2017: Amino Acids
https://www.readbyqxmd.com/read/28651991/ribosome-inactivating-proteins-from-an-evolutionary-perspective
#6
Walter Jesús Lapadula, Maximiliano Juri Ayub
Ribosome Inactivating Proteins (RIPs) are rRNA N-glycosidases that inhibit protein synthesis through the elimination of a single adenine residue from 28S rRNA. Many of these toxins have been characterized in depth from a biochemical and molecular point of view. In addition, their potential use in medicine as highly selective toxins is being explored. In contrast, the evolutionary history of RIP encoding genes has remained traditionally underexplored. In recent years, accumulation of large genomic data has fueled research on this issue and revealed unexpected information about the origin and evolution of RIP toxins...
June 24, 2017: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/28637748/impaired-spliceosomal-usnrnp-assembly-leads-to-sm-mrna-down-regulation-and-sm-protein-degradation
#7
Archana Bairavasundaram Prusty, Rajyalakshmi Meduri, Bhupesh Kumar Prusty, Jens Vanselow, Andreas Schlosser, Utz Fischer
Specialized assembly factors facilitate the formation of many macromolecular complexes in vivo. The formation of Sm core structures of spliceosomal U-rich small nuclear ribonucleoprotein particles (UsnRNPs) requires assembly factors united in protein arginine methyltransferase 5 (PRMT5) and survival motor neuron (SMN) complexes. We demonstrate that perturbations of this assembly machinery trigger complex cellular responses that prevent aggregation of unassembled Sm proteins. Inactivation of the SMN complex results in the initial tailback of Sm proteins on the PRMT5 complex, followed by down-regulation of their encoding mRNAs...
June 21, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28600528/overexpression-of-rasd1-inhibits-glioma-cell-migration-invasion-and-inactivates-the-akt-mtor-signaling-pathway
#8
Shangfeng Gao, Lei Jin, Guangping Liu, Peng Wang, Zonghan Sun, Yujia Cao, Hengliang Shi, Xuejiao Liu, Qiong Shi, Xiuping Zhou, Rutong Yu
The RAS signaling pathway is hyperactive in malignant glioma due to overexpression and/or increased activity. A previous study identified that RASD1, a member of the RAS superfamily of small G-proteins, is a significantly dysregulated gene in oligodendroglial tumors that responded to chemotherapy. However, the role and mechanism of RASD1 in the progression of human glioma remain largely unknown. In the present study, by analyzing a public genomics database, we found that high levels of RASD1 predicted good survival of astrocytoma patients...
June 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28599209/modelling-toxin-effects-on-protein-biosynthesis-in-eukaryotic-cells
#9
Vladas Skakauskas, Pranas Katauskis
We present a rather generic model for toxin (ricin) inhibition of protein biosynthesis in eukaryotic cells. We also study reduction of the ricin toxic effects with application of antibodies against the RTB subunit of ricin molecules. Both species initially are delivered extracellularly. The model accounts for the pinocytotic and receptor-mediated toxin endocytosis and the intact toxin exocytotic removal out of the cell. The model also includes the lysosomal toxin destruction, the intact toxin motion to the endoplasmic reticulum (ER) for separation of its molecules into the RTA and RTB subunits, and the RTA chain translocation into the cytosol...
May 31, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28544148/structure-and-biosynthesis-of-crocagins-polycyclic-postranslationally-modified-ribosomal-peptides-from-chondromyces-crocatus
#10
Konrad Viehrig, Frank Surup, Carsten Volz, Jennifer Herrmann, Antoine Abou Fayad, Sebastian Adam, Jesko Köhnke, Dirk Trauner, Rolf Müller
Secondary metabolome mining efforts in the myxobacterial multiproducer of natural products, Chondromyces crocatus Cm c5, resulted in the isolation and structure elucidation of crocagins, which are novel polycyclic peptides containing a tetrahydropyrrolo[2,3-b]indole core. The gene cluster was identified through an approach combining genome analysis, targeted gene inactivation in the producer, and in vitro experiments. Based on our findings, we developed a biosynthetic scheme for crocagin biosynthesis. These natural products are formed from the three C-terminal amino acids of a precursor peptide and thus belong to a novel class of ribosomally synthesized and post-translationally modified peptides (RiPPs)...
May 23, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28536379/plant-toxin-based-immunotoxins-for-cancer-therapy-a-short-overview
#11
REVIEW
Letizia Polito, Alice Djemil, Massimo Bortolotti
Immunotoxins are chimeric proteins obtained by linking a toxin to either an intact antibody or an antibody fragment. Conjugation can be obtained by chemical or genetic engineering, where the latter yields recombinant conjugates. An essential requirement is that the target molecule recognized by the antibody is confined to the cell population to be deleted, or at least that it is not present on stem cells or other cell types essential for the organism's survival. Hundreds of different studies have demonstrated the potential for applying immunotoxins to many models in pre-clinical studies and in clinical trials...
June 1, 2016: Biomedicines
https://www.readbyqxmd.com/read/28512335/arginine-rich-cell-penetrating-peptide-modified-extracellular-vesicles-for-active-macropinocytosis-induction-and-efficient-intracellular-delivery
#12
Ikuhiko Nakase, Kosuke Noguchi, Ayako Aoki, Tomoka Takatani-Nakase, Ikuo Fujii, Shiroh Futaki
Extracellular vesicles (EVs) including exosomes have been shown to play crucial roles in cell-to-cell communication because of their ability to carry biofunctional molecules (e.g., microRNAs and enzymes). EVs also have pharmaceutical advantages and are highly anticipated to be a next-generation intracellular delivery tool. Here, we demonstrate an experimental technique that uses arginine-rich cell-penetrating peptide (CPP)-modified EVs to induce active macropinocytosis for effective cellular EV uptake. Modification of arginine-rich CPPs on the EV membrane resulted in the activation of the macropinocytosis pathway, and the number of arginine residues in the peptide sequences affected the cellular EV uptake efficiency...
May 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28501939/dianthin-30-or-gelonin-versus-monomethyl-auristatin-e-each-configured-with-an-anti-calcitonin-receptor-antibody-are-differentially-potent-in-vitro-in-high-grade-glioma-cell-lines-derived-from-glioblastoma
#13
Roger Gilabert-Oriol, Sebastian G B Furness, Brett W Stringer, Alexander Weng, Hendrik Fuchs, Bryan W Day, Angela Kourakis, Andrew W Boyd, David L Hare, Mayank Thakur, Terrance G Johns, Peter J Wookey
We have reported that calcitonin receptor (CTR) is widely expressed in biopsies from the lethal brain tumour glioblastoma by malignant glioma and brain tumour-initiating cells (glioma stem cells) using anti-human CTR antibodies. A monoclonal antibody against an epitope within the extracellular domain of CTR was raised (mAb2C4) and chemically conjugated to either plant ribosome-inactivating proteins (RIPs) dianthin-30 or gelonin, or the drug monomethyl auristatin E (MMAE), and purified. In the high-grade glioma cell line (HGG, representing glioma stem cells) SB2b, in the presence of the triterpene glycoside SO1861, the EC50 for mAb2C4:dianthin was 10...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28500327/metazoan-ribosome-inactivating-protein-encoding-genes-acquired-by-horizontal-gene-transfer
#14
Walter J Lapadula, Paula L Marcet, María L Mascotti, M Virginia Sanchez-Puerta, Maximiliano Juri Ayub
Ribosome inactivating proteins (RIPs) are RNA N-glycosidases that depurinate a specific adenine residue in the conserved sarcin/ricin loop of 28S rRNA. These enzymes are widely distributed among plants and their presence has also been confirmed in several bacterial species. Recently, we reported for the first time in silico evidence of RIP encoding genes in metazoans, in two closely related species of insects: Aedes aegypti and Culex quinquefasciatus. Here, we have experimentally confirmed the presence of these genes in mosquitoes and attempted to unveil their evolutionary history...
May 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28460437/trichosanthin-increases-granzyme-b-penetration-into-tumor-cells-by-upregulation-of-ci-mpr-on-the-cell-surface
#15
Chunman Li, Meiqi Zeng, Huju Chi, Jing Shen, Tzi-Bun Ng, Guangyi Jin, Desheng Lu, Xinmin Fan, Bilian Xiong, Zhangang Xiao, Ou Sha
Trichosanthin is a plant toxin belonging to the family of ribosome-inactivating proteins. It has various biological and pharmacological activities, including anti-tumor and immunoregulatory effects. In this study, we explored the potential medicinal applications of trichosanthin in cancer immunotherapy. We found that trichosanthin and cation-independent mannose-6-phosphate receptor competitively bind to the Golgi-localized, γ-ear containing and Arf-binding proteins. It in turn promotes the translocation of cation-independent mannose-6-phosphate receptor from the cytosol to the plasma membrane, which is a receptor of Granzyme B...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445155/retinoblastoma-cells-activate-the-akt-pathway-and-are-vulnerable-to-the-pi3k-mtor-inhibitor-nvp-bez235
#16
Chencheng Xie, Matthew J Freeman, Huarui Lu, Xiaohong Wang, Colleen L Forster, Aaron L Sarver, Timothy C Hallstrom
Retinoblastoma is a pediatric cancer of the retina most often caused by inactivation of the retinoblastoma (RB1) tumor suppressor gene. We previously showed that Rb1 loss cooperates with either co-activating the phosphatidylinositol 3-kinase (PI3K)/AKT pathway, or co-deleting Pten, to initiate retinoblastoma tumors in mice. The objectives of this study were to determine if the AKT pathway is activated in human retinoblastomas and the extent that anti-PI3K therapy induces apoptosis in retinoblastoma cells, alone or in combination with the DNA damaging drugs carboplatin and topotecan...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28414205/molecular-tumor-targeting-of-gelonin-by-fusion-with-f3-peptide
#17
Song-Hee Ham, Kyoung Ah Min, Meong Cheol Shin
Therapeutically potent macromolecular drugs have shown great promise for overcoming the limitations of small-molecule anti-cancer drugs. But tumor cell-selective intracellular delivery of the macromolecules remains a major hurdle for their successful clinical application. To overcome this challenge, we engineered a novel genetic fusion protein (F3-Gel) that composed of F3 peptide, a tumor-homing peptide, and gelonin, a plant-derived ribosome-inactivating protein (RIP), and then evaluated its anti-cancer activity in vitro and in vivo...
June 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28389897/novel-purification-method-and-antibiotic-activity-of-recombinant-momordica-charantia-map30
#18
Ching-Dong Chang, Ping-Yuan Lin, Yo-Chia Chen, Han-Hsiang Huang, Wen-Ling Shih
Ribosome-inactivating proteins (RIPs) are a group of enzymes originally isolated from plants that possess the ability to damage ribosomes in an irreversible manner, leading to inhibition of protein synthesis in eukaryotic cells. In this study, we aimed to purify recombinant RIPs, investigate their function in the treatment of bacterial infection, and determine their toxicity in mice. We employed a pMAL protein fusion and purification system using E. coli transformed with a plasmid containing MBP-tagged MAP30 cDNA...
May 2017: 3 Biotech
https://www.readbyqxmd.com/read/28378131/balsamin-induces-apoptosis-in-breast-cancer-cells-via-dna-fragmentation-and-cell-cycle-arrest
#19
Parminder K Ajji, Marley J Binder, Ken Walder, Munish Puri
Breast cancer is the second most common cancer causing death worldwide with metastasis and disease relapse being the major drawbacks in current treatments. Therefore, development of novel drugs is needed. Balsamin, a 28 kDa Type I ribosome-inactivating protein, is rich in the seeds of Momordica balsamina. In this study, the molecular mechanism and the possible effects of balsamin on the two key hallmarks of cancer were investigated. Firstly, the induction of apoptosis in human breast cancer MCF-7 and BT549 cells showed that balsamin-induced apoptosis involved increases in caspase-3 and caspase-8 activity, upregulation of Bax, Bid, and Bad, and downregulation of BCL-2 and BCL-XL...
April 4, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28365881/a-comparison-between-constitutive-and-inducible-transgenic-expression-of-the-phrip-i-gene-for-broad-spectrum-resistance-against-phytopathogens-in-potato
#20
Romel Gonzales-Salazar, Bianca Cecere, Michelina Ruocco, Rosa Rao, Giandomenico Corrado
OBJECTIVES: To engineer broad spectrum resistance in potato using different expression strategies. RESULTS: The previously identified Ribosome-Inactivating Protein from Phytolacca heterotepala was expressed in potato under a constitutive or a wound-inducible promoter. Leaves and tubers of the plants constitutively expressing the transgene were resistant to Botrytis cinerea and Rhizoctonia solani, respectively. The wound-inducible promoter was useful in driving the expression upon wounding and fungal damage, and conferred resistance to B...
April 1, 2017: Biotechnology Letters
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