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ribosome inactivating protein

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https://www.readbyqxmd.com/read/28600528/overexpression-of-rasd1-inhibits-glioma-cell-migration-invasion-and-inactivates-the-akt-mtor-signaling-pathway
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28365058/impact-of-high-hydrostatic-pressure-on-bacterial-proteostasis
#14
Elisa Gayán, Sander K Govers, Abram Aertsen
High hydrostatic pressure (HHP) is an important factor that limits microbial growth in deep-sea ecosystems to specifically adapted piezophiles. Furthermore, HHP treatment is used as a novel food preservation technique because of its ability to inactivate pathogenic and spoilage bacteria while minimizing the loss of food quality. Disruption of protein homeostasis (i.e. proteostasis) as a result of HHP-induced conformational changes in ribosomes and proteins has been considered as one of the limiting factors for both microbial growth and survival under HHP conditions...
March 21, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28359823/tandem-multimeric-f3-gelonin-fusion-toxins-for-enhanced-anti-cancer-activity-for-prostate-cancer-treatment
#15
Meong Cheol Shin, Kyoung Ah Min, Heesun Cheong, Cheol Moon, Yongzhuo Huang, Huining He, Victor C Yang
Despite significant progress in prostate cancer treatment, yet, it remains the leading diagnosed cancer and is responsible for high incidence of cancer related deaths in the U.S. Because of the insufficient efficacy of small molecule anti-cancer drugs, significant interest has been drawn to more potent macromolecular agents such as gelonin, a plant-derived ribosome inactivating protein (RIP) that efficiently inhibits protein translation. However, in spite of the great potency to kill tumor cells, gelonin lacks ability to internalize tumor cells and furthermore, cannot distinguish between tumor and normal cells...
March 27, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28357420/smi-ribosome-inactivating-protein-conjugates-selectively-inhibit-tumor-cell-growth
#16
Saumya Roy, Jun Y Axup, Jane S Forsyth, Rajib K Goswami, Benjamin M Hutchins, Krishna M Bajuri, Stephanie A Kazane, Vaughn V Smider, Brunhilde H Felding, Subhash C Sinha
Cell-targeting conjugates of Saporin 6, a ribosome inactivating protein (RIP), were prepared using the Saporin Ala 157 Cys mutant, a small molecule inhibitor (SMI) of integrins αvβ3/αvβ5, and a potent cytotoxin, auristatin F (AF). The conjugates selectively and potently inhibited proliferation of tumor cells expressing the target integrins. We anticipate that the small molecule-RIP bioconjugate approach can be broadly applied using other small molecule drugs.
April 11, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28353660/extensive-evolution-of-cereal-ribosome-inactivating-proteins-translates-into-unique-structural-features-activation-mechanisms-and-physiological-roles
#17
REVIEW
Jeroen De Zaeytijd, Els J M Van Damme
Ribosome-inactivating proteins (RIPs) are a class of cytotoxic enzymes that can depurinate rRNAs thereby inhibiting protein translation. Although these proteins have also been detected in bacteria, fungi, and even some insects, they are especially prevalent in the plant kingdom. This review focuses on the RIPs from cereals. Studies on the taxonomical distribution and evolution of plant RIPs suggest that cereal RIPs have evolved at an enhanced rate giving rise to a large and heterogeneous RIP gene family. Furthermore, several cereal RIP genes are characterized by a unique domain architecture and the lack of a signal peptide...
March 29, 2017: Toxins
https://www.readbyqxmd.com/read/28336682/molecular-mechanism-of-mrna-repression-in-trans-by-a-proq-dependent-small-rna
#18
Alexandre Smirnov, Chuan Wang, Lisa L Drewry, Jörg Vogel
Research into post-transcriptional control of mRNAs by small noncoding RNAs (sRNAs) in the model bacteria Escherichia coli and Salmonella enterica has mainly focused on sRNAs that associate with the RNA chaperone Hfq. However, the recent discovery of the protein ProQ as a common binding partner that stabilizes a distinct large class of structured sRNAs suggests that additional RNA regulons exist in these organisms. The cellular functions and molecular mechanisms of these new ProQ-dependent sRNAs are largely unknown...
April 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28320279/plasticity-of-central-and-peripheral-sources-of-noradrenaline-in-rats-during-ontogenesis
#19
N S Bondarenko, L K Dilmukhametova, A Yu Kurina, A R Murtazina, A Ya Sapronova, A P Sysoeva, M V Ugrumov
The morphogenesis of individual organs and the whole organism occurs under the control of intercellular chemical signals mainly during the perinatal period of ontogenesis in rodents. In this study, we tested our hypothesis that the biologically active concentration of noradrenaline (NA) in blood in perinatal ontogenesis of rats is maintained due to humoral interaction between its central and peripheral sources based on their plasticity. As one of the mechanisms of plasticity, we examined changes in the secretory activity (spontaneous and stimulated release of NA) of NA-producing organs under deficiency of its synthesis in the brain...
March 2017: Biochemistry. Biokhimii︠a︡
https://www.readbyqxmd.com/read/28301598/regulation-of-anti-apoptotic-bcl-2-family-protein-mcl-1-by-s6-kinase-2
#20
Alakananda Basu, Savitha Sridharan
The anti-apoptotic Bcl-2 family protein myeloid cell leukemia-1 (Mcl-1) plays an important role in breast cancer cell survival and chemoresistance. We have previously shown that knockdown of the 40S ribosomal protein S6 kinase-2 (S6K2), which acts downstream of the mechanistic target of rapamycin complex 1 (mTORC1), enhanced breast cancer cell death by apoptotic stimuli. The increase in cell death by S6K2 depletion was partly due to inactivation of Akt. In the present study, we investigated if S6K2 regulates Mcl-1, which acts downstream of Akt...
2017: PloS One
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