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ribosome inactivating protein

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https://www.readbyqxmd.com/read/29133924/bio-detoxification-of-ricin-in-castor-bean-ricinus-communis-l-seeds
#1
Natália L Sousa, Glaucia B Cabral, Pabline M Vieira, Aisy B Baldoni, Francisco J L Aragão
Ricin is a highly toxic ribosome-inactivating lectin occurring in the seeds of castor bean (Ricinus communis L.). Castor bean grows throughout tropical and sub-tropical regions and is a very important crop due to its high seed content of ricinoleic acid, an unusual fatty acid, which has several industrial applications. However, due to the presence of the toxin, castor bean can cause death after the exposure of animals to low doses of ricin through skin contact, injection, inhalation or oral routes. Aiming to generate a detoxified genotype, we explored the RNAi concept in order to silence the ricin coding genes in the endosperm of castor bean seeds...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29107534/m-6-a-facilitates-eif4f-independent-mrna-translation
#2
Ryan A Coots, Xiao-Min Liu, Yuanhui Mao, Leiming Dong, Jun Zhou, Ji Wan, Xingqian Zhang, Shu-Bing Qian
In eukaryotic cells, protein synthesis typically begins with the binding of eIF4F to the 7-methylguanylate (m(7)G) cap found on the 5' end of the majority of mRNAs. Surprisingly, overall translational output remains robust under eIF4F inhibition. The broad spectrum of eIF4F-resistant translatomes is incompatible with cap-independent translation mediated by internal ribosome entry sites (IRESs). Here, we report that N(6)-methyladenosine (m(6)A) facilitates mRNA translation that is resistant to eIF4F inactivation...
October 23, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29107333/granzyme-b-disrupts-central-metabolism-and-protein-synthesis-in-bacteria-to-promote-an-immune-cell-death-program
#3
Farokh Dotiwala, Sumit Sen Santara, Andres Ariel Binker-Cosen, Bo Li, Sriram Chandrasekaran, Judy Lieberman
Human cytotoxic lymphocytes kill intracellular microbes. The cytotoxic granule granzyme proteases released by cytotoxic lymphocytes trigger oxidative bacterial death by disrupting electron transport, generating superoxide anion and inactivating bacterial oxidative defenses. However, they also cause non-oxidative cell death because anaerobic bacteria are also killed. Here, we use differential proteomics to identify granzyme B substrates in three unrelated bacteria: Escherichia coli, Listeria monocytogenes, and Mycobacteria tuberculosis...
October 25, 2017: Cell
https://www.readbyqxmd.com/read/29104238/which-plant-proteins-are-involved-in-antiviral-defense-review-on-in-vivo-and-in-vitro-activities-of-selected-plant-proteins-against-viruses
#4
REVIEW
Oskar Musidlak, Robert Nawrot, Anna Goździcka-Józefiak
Plants have evolved a variety of defense mechanisms to tackle virus attack. Endogenous plant proteins can function as virus suppressors. Different types of proteins mediate defense responses against plant viruses. Pathogenesis-related (PR) proteins are activated upon pathogen infections or in different stress situations and their production is one of many components in plant defense. Ribosome-inactivating proteins (RIPs) suppress translation by enzymatically damaging ribosomes and they have been found to have antiviral activity...
November 1, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29076988/the-use-of-plant-derived-ribosome-inactivating-proteins-in-immunotoxin-development-past-present-and-future-generations
#5
REVIEW
Aleksander Rust, Lynda J Partridge, Bazbek Davletov, Guillaume M Hautbergue
Ribosome inactivating proteins (RIPs) form a class of toxins that was identified over a century ago. They continue to fascinate scientists and the public due to their very high activity and long-term stability which might find useful applications in the therapeutic killing of unwanted cells but can also be used in acts of terror. We will focus our review on the canonical plant-derived RIPs which display ribosomal RNA N-glycosidase activity and irreversibly inhibit protein synthesis by cleaving the 28S ribosomal RNA of the large 60S subunit of eukaryotic ribosomes...
October 27, 2017: Toxins
https://www.readbyqxmd.com/read/29064680/plant-translation-initiation-complex-eifiso4f-directs-pokeweed-antiviral-protein-to-selectively-depurinate-uncapped-tobacco-etch-virus-rna
#6
Artem V Domashevskiy, Shawn Williams, Christopher Kluge, Shu-Yuan Cheng
Pokeweed antiviral protein (PAP) is a ribosome inactivating protein (RIP) that depurinates the sarcin/ricin loop (SRL) of rRNA, inhibiting protein synthesis. PAP depurinates viral RNA, and in doing so, lowers the infectivity of many plant viruses. The mechanism by which PAP accesses uncapped viral RNA is not known, impeding scientists from developing effective antiviral agents for the prevention of the diseases caused by uncapped RNA viruses. Kinetic rates of PAP interacting with tobacco etch virus (TEV) RNA, in the presence and absence of eIFiso4F, were examined, addressing how the eIF affects selective PAP targeting and depurination of the uncapped viral RNA...
November 1, 2017: Biochemistry
https://www.readbyqxmd.com/read/29057799/a-monoclonal-monoclonal-antibody-based-capture-elisa-for-abrin
#7
Christina C Tam, Luisa W Cheng, Xiaohua He, Paul Merrill, David Hodge, Larry H Stanker
Abrin, one of the most highly potent toxins in the world, is derived from the plant, Abrus precatorius. Because of its high toxicity, it poses potential bioterror risks. Therefore, a need exists for new reagents and technologies that would be able to rapidly detect abrin contamination as well as lead to new therapeutics. We report here a group of abrin-specific monoclonal antibodies (mAbs) that recognize abrin A-chain, intact A-B chain toxin, and agglutinin by Western blot. Additionally, these mAbs were evaluated for their ability to serve as capture antibodies for a sandwich (capture) ELISA...
October 18, 2017: Toxins
https://www.readbyqxmd.com/read/29023422/plant-ribosome-inactivating-proteins-progesses-challenges-and-biotechnological-applications-and-a-few-digressions
#8
REVIEW
Maria Serena Fabbrini, Miku Katayama, Ikuhiko Nakase, Riccardo Vago
Plant ribosome-inactivating protein (RIP) toxins are EC3.2.2.22 N-glycosidases, found among most plant species encoded as small gene families, distributed in several tissues being endowed with defensive functions against fungal or viral infections. The two main plant RIP classes include type I (monomeric) and type II (dimeric) as the prototype ricin holotoxin from Ricinus communis that is composed of a catalytic active A chain linked via a disulphide bridge to a B-lectin domain that mediates efficient endocytosis in eukaryotic cells...
October 12, 2017: Toxins
https://www.readbyqxmd.com/read/28947655/mechanistic-insights-in-x-chromosome-inactivation
#9
REVIEW
Zhipeng Lu, Ava C Carter, Howard Y Chang
X-chromosome inactivation (XCI) is a critical epigenetic mechanism for balancing gene dosage between XY males and XX females in eutherian mammals. A long non-coding RNA (lncRNA), XIST, and its associated proteins orchestrate this multi-step process, resulting in the inheritable silencing of one of the two X-chromosomes in females. The XIST RNA is large and complex, exemplifying the unique challenges associated with the structural and functional analysis of lncRNAs. Recent technological advances in the analysis of macromolecular structure and interactions have enabled us to systematically dissect the XIST ribonucleoprotein complex, which is larger than the ribosome, and its place of action, the inactive X-chromosome...
November 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28932186/da-negatively-regulates-igf-i-actions-implicated-in-cognitive-function-via-interaction-of-psd95-and-nnos-in-minimal-hepatic-encephalopathy
#10
Saidan Ding, Weishan Zhuge, Xuebao Wang, Jianjing Yang, Yuanshao Lin, Chengde Wang, Jiangnan Hu, Qichuan Zhuge
Insulin-like growth factor I (IGF-I) has been positively correlated with cognitive ability. Cognitive decline in minimal hepatic encephalopathy (MHE) was shown to be induced by elevated intracranial dopamine (DA). The beneficial effect of IGF-I signaling in MHE remains unknown. In this study, we found that IGF-I content was reduced in MHE rats and that IGF-I administration mitigated cognitive decline of MHE rats. A protective effect of IGF-I on the DA-induced interaction between postsynaptic density protein 95 (PSD95) and neuronal nitric oxide synthase (nNOS) was found in neurons...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28928861/down-regulation-of-rps9-inhibits-osteosarcoma-cell-growth-through-inactivation-of-mapk-signaling-pathway
#11
Dong-Dong Cheng, Bin Zhu, Shi-Jie Li, Ting Yuan, Qing-Cheng Yang, Cun-Yi Fan
Objectives: Osteosarcoma is the most common malignant bone tumor in adolescents; however, the mechanisms involved in the pathogenesis and progression of osteosarcoma remain to be elucidated. Researchers have provided valuable insights into the tumorigenesis of Ribosomal protein S9 (RPS9) in some cancers. The purpose of this study was to elucidate the expression, functions, and mechanisms of RPS9 in human osteosarcoma. Methods: The expression of RPS9 in osteosarcoma tissues and cell lines was evaluated by qRT-PCR and western blotting...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28919908/hepatic-s6k1-partially-regulates-lifespan-of-mice-with-mitochondrial-complex-i-deficiency
#12
Takashi K Ito, Chenhao Lu, Jacob Khan, Quy Nguyen, Heather Z Huang, Dayae Kim, James Phillips, Jo Tan, Yenna Lee, Tuyet Nguyen, Samy Khessib, Natalie Lim, Surapat Mekvanich, Joshua Oh, Victor V Pineda, Weirong Wang, Alessandro Bitto, Jonathan Y An, John F Morton, Mitsutoshi Setou, Warren C Ladiges, Matt Kaeberlein
The inactivation of ribosomal protein S6 kinase 1 (S6K1) recapitulates aspects of caloric restriction and mTORC1 inhibition to achieve prolonged longevity in invertebrate and mouse models. In addition to delaying normative aging, inhibition of mTORC1 extends the shortened lifespan of yeast, fly, and mouse models with severe mitochondrial disease. Here we tested whether disruption of S6K1 can recapitulate the beneficial effects of mTORC1 inhibition in the Ndufs4 knockout (NKO) mouse model of Leigh Syndrome caused by Complex I deficiency...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28912890/glioma-dual-targeting-nanohybrid-protein-toxin-constructed-by-intein-mediated-site-specific-ligation-for-multistage-booster-delivery
#13
Yingzhi Chen, Meng Zhang, Hongyue Jin, Dongdong Li, Fan Xu, Aihua Wu, Jinyu Wang, Yongzhuo Huang
Malignant glioma is one of the most untreatable cancers because of the formidable blood-brain barrier (BBB), through which few therapeutics can penetrate and reach the tumors. Biologics have been booming in cancer therapy in the past two decades, but their application in brain tumor has long been ignored due to the impermeable nature of BBB against effective delivery of biologics. Indeed, it is a long unsolved problem for brain delivery of macromolecular drugs, which becomes the Holy Grail in medical and pharmaceutical sciences...
2017: Theranostics
https://www.readbyqxmd.com/read/28911628/antifungal-activity-of-momordica-charantia-seed-extracts-toward-the-pathogenic-fungus-fusarium-solani-l
#14
Shuzhen Wang, Yongliang Zheng, Fu Xiang, Shiming Li, Guliang Yang
Momordica charantia L., a vegetable crop with high nutritional value, has been used as an antimutagenic, antihelminthic, anticancer, antifertility, and antidiabetic agent in traditional folk medicine. In this study, the antifungal activity of M. charantia seed extract toward Fusarium solani L. was evaluated. Results showed that M. charantia seed extract effectively inhibited the mycelial growth of F. solani, with a 50% inhibitory rate (IC50) value of 108.934 μg/mL. Further analysis with optical microscopy and fluorescence microscopy revealed that the seed extract led to deformation of cells with irregular budding, loss of integrity of cell wall, as well as disruption of the fungal cell membrane...
October 2016: Journal of Food and Drug Analysis
https://www.readbyqxmd.com/read/28904868/high-density-lipoprotein-protects-cardiomyocytes-from-oxidative-stress-via-the-pi3k-mtor-signaling-pathway
#15
Manabu Nagao, Ryuji Toh, Yasuhiro Irino, Hideto Nakajima, Toshihiko Oshita, Shigeyasu Tsuda, Tetsuya Hara, Masakazu Shinohara, Tatsuro Ishida, Ken-Ichi Hirata
Low levels of plasma high-density lipoprotein (HDL) cholesterol are associated with an increased risk of heart failure, regardless of the presence or absence of coronary artery disease. However, the direct effects of HDL on failing myocardium have not been fully elucidated. We found that HDL treatment resulted in improved cell viability in H9c2 cardiomyocytes under oxidative stress. This cardioprotective effect of HDL was regulated via the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway...
September 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28900896/fusion-of-gelonin-and-anti-insulin-like-growth-factor-1-receptor-igf-1r-affibody-for-enhanced-brain-cancer-therapy
#16
Songhee Ham, Kyoung Ah Min, Jae Wook Yang, Meong Cheol Shin
Owing to the extraordinary potency in inhibiting protein translation that could eventually lead to apoptosis of tumor cells, ribosome-inactivating proteins (RIPs) such as gelonin have been considered attractive drug candidates for cancer therapy. However, due to several critical obstacles (e.g., severe toxicity issues caused by a lack of selectivity in their mode of action and the low cytotoxicity via poor cellular uptake, etc.), clinical application of RIPs is yet far from being accomplished. To overcome these challenges, in the present study, we engineered gelonin fusion proteins with anti-insulin-like growth factor-1 receptor (IGF-1R) affibody ("IAFF") via the genetic recombinant method and the SpyCatcher/SpyTag-mediated conjugation method...
September 12, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/28880866/ribosomal-dna-copy-number-amplification-and-loss-in-human-cancers-is-linked-to-tumor-genetic-context-nucleolus-activity-and-proliferation
#17
Meng Wang, Bernardo Lemos
Ribosomal RNAs (rRNAs) are transcribed from two multicopy DNA arrays: the 5S ribosomal DNA (rDNA) array residing in a single human autosome and the 45S rDNA array residing in five human autosomes. The arrays are among the most variable segments of the genome, exhibit concerted copy number variation (cCNV), encode essential components of the ribosome, and modulate global gene expression. Here we combined whole genome data from >700 tumors and paired normal tissues to provide a portrait of rDNA variation in human tissues and cancers of diverse mutational signatures, including stomach and lung adenocarcinomas, ovarian cancers, and others of the TCGA panel...
September 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28835357/activation-of-%C3%AE-2-ampk-suppresses-ribosome-biogenesis-and-protects-against-myocardial-ischemia-reperfusion-injury
#18
Yang Cao, Naveen Bojjireddy, Maengjo Kim, Tao Li, Peiyong Zhai, Narayani Nagarajan, Junichi Sadoshima, Richard D Palmiter, Rong Tian
RATIONALE: AMPK (AMP-activated protein kinase) is a heterotrimeric protein that plays an important role in energy homeostasis and cardioprotection. Two isoforms of each subunit are expressed in the heart, but the isoform-specific function of AMPK remains unclear. OBJECTIVE: We sought to determine the role of γ2-AMPK in cardiac stress response using bioengineered cell lines and mouse models containing either isoform of the γ-subunit in the heart. METHODS AND RESULTS: We found that γ2 but not γ1 or γ3 subunit translocated into nucleus on AMPK activation...
October 27, 2017: Circulation Research
https://www.readbyqxmd.com/read/28831158/inhibition-of-post-transcriptional-steps-in-ribosome-biogenesis-confers-cytoprotection-against-chemotherapeutic-agents-in-a-p53-dependent-manner
#19
Russell T Sapio, Anastasiya N Nezdyur, Matthew Krevetski, Leonid Anikin, Vincent J Manna, Natalie Minkovsky, Dimitri G Pestov
The p53-mediated nucleolar stress response associated with inhibition of ribosomal RNA transcription was previously shown to potentiate killing of tumor cells. Here, we asked whether targeting of ribosome biogenesis can be used as the basis for selective p53-dependent cytoprotection of nonmalignant cells. Temporary functional inactivation of the 60S ribosome assembly factor Bop1 in a 3T3 cell model markedly increased cell recovery after exposure to camptothecin or methotrexate. This was due, at least in part, to reversible pausing of the cell cycle preventing S phase associated DNA damage...
August 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820908/ribosomopathy-like-properties-of-murine-and-human-cancers
#20
Sucheta Kulkarni, James M Dolezal, Huabo Wang, Laura Jackson, Jie Lu, Brian P Frodey, Atinuke Dosunmu-Ogunbi, Youjun Li, Marc Fromherz, Audry Kang, Lucas Santana-Santos, Panayiotis V Benos, Edward V Prochownik
Ribosomopathies comprise a heterogeneous group of hematologic and developmental disorders, often characterized by bone marrow failure, skeletal and other developmental abnormalities and cancer predisposition. They are associated with mutations and/or haplo-insufficiencies of ribosomal proteins (RPs) and inefficient ribosomal RNA (rRNA) processing. The resulting ribosomal stress induces the canonical p19ARF/Mdm2/p53 tumor suppressor pathway leading to proliferative arrest and/or apoptosis. It has been proposed that this pathway is then inactivated during subsequent neoplastic evolution...
2017: PloS One
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