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ribosome inactivating protein

Ziling Fang, Bo Cao, Jun-Ming Liao, Jun Deng, Kevin D Plummer, Peng Liao, Tao Liu, Wensheng Zhang, Kun Zhang, Li Li, David Margolin, Shelya X Zeng, Jianping Xiong, Hua Lu
Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of human cancer cells. Mechanistically, SPIN1 sequesters uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity towards p53...
March 16, 2018: ELife
Stephanie C Casey, Virginie Baylot, Dean W Felsher
The MYC proto-oncogene is a gene product that coordinates the transcriptional regulation of a multitude of genes that are essential to cellular programs required for normal as well as neoplastic cellular growth and proliferation, including cell cycle, self-renewal, survival, cell growth, metabolism, protein and ribosomal biogenesis, and differentiation. Here we propose that MYC regulates these programs in a manner that is coordinated with a global influence on the host immune response. MYC had been presumed to contribute to tumorigenesis through tumor cell intrinsic influences...
March 7, 2018: Blood
Tung-Chen Yeh, Ching-Sen Shin, Hsin-Hung Chen, Chi-Cheng Lai, Gwo-Ching Sun, Ching-Jiunn Tseng, Pei-Wen Cheng
Resveratrol is a polyphenol with pleiotropic effects against oxidative damage that has been widely implicated in the lowering of hypertension risk. The purpose of this study was to determine whether improve NO release in the brain either through the activation of AMPK or reduced Rac1-induced ROS generation, thereby reducing BP in rats with fructose-induced hypertension. The rats were fed with 10% fructose or crestor (rosuvastatin; 1.5 mg/kg/day) and resveratrol (10 mg/kg/day) treatment for 1 week, the systolic blood pressure (SBP) of the rats were measured by tail-cuff method...
March 1, 2018: Journal of Applied Physiology
Bee Gek Ng, Jae Woo Han, Dong Wan Lee, Gyung Ja Choi, Beom Seok Kim
Hahella chejuensis MB-1084 is a Gram-negative marine bacterial strain that produces unusual 17-membered carbocyclic tetraenes, chejuenolide A and B. Two fosmid clones responsible for chejuenolide production were identified from the genomic DNA library of the MB-1084 strain. Systematic inactivation of the open reading frames (ORFs) in the sequenced region defines the boundaries of the chejuenolide (che) biosynthetic gene cluster (24.9 kbp) that encodes one non-ribosomal peptide synthase (NRPS)-polyketide synthase (PKS) hybrid protein, three modular PKSs, two PKS domains, and an amine oxidase homolog...
February 26, 2018: Journal of Antibiotics
Simko Sama, Eric Woith, Wolfgang Walther, Gerold Jerz, Wei Chen, Stephen Hart, Matthias F Melzig, Alexander Weng
Neuroblastoma represents the third most common malign neoplasm occurring in children and the most common in newborn. Although mortality in childhood cancer declined in the last decade, high-risk patients have poor prospects, due to the aggressiveness of the cancer. In the recent past, we underlined the potential of sapofectosid as novel and efficient transfection enhancer, demonstrating non-toxic gene delivery, but its value in tumor therapies has yet to be elucidated. A suicide gene, coding for saporin, a ribosome-inactivating protein type I, was incorporated into targeted, peptide-based nanoplexes...
February 23, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Feng Zhu, Yang-Kai Zhou, Zhao-Lin Ji, Xiao-Ren Chen
Ribosome-inactivating proteins (RIPs) are toxic N -glycosidases that depurinate eukaryotic and prokaryotic rRNAs, thereby arresting protein synthesis during translation. RIPs are widely found in various plant species and within different tissues. It is demonstrated in vitro and in transgenic plants that RIPs have been connected to defense by antifungal, antibacterial, antiviral, and insecticidal activities. However, the mechanism of these effects is still not completely clear. There are a number of reviews of RIPs...
2018: Frontiers in Plant Science
Parminder K Ajji, Shailendra P Sonkar, Ken Walder, Munish Puri
Balsamin, a type I ribosome-inactivating protein (RIP), has been shown to inhibit HIV-1 replication at the translation step. Our recent studies have shown that balsamin also possess anti-tumor, antibacterial and DNase-like activity, however, the amount of natural balsamin in Momordica balsamina seeds is limited and preclinical studies require large quantities of pure, bioactive balsamin. Therefore, in this study, we cloned the balsamin gene, expressed it in E. coli BL21(DE3) strain and purified it by nickel affinity chromatography...
February 19, 2018: International Journal of Biological Macromolecules
Haruhiko Jimbo, Rayakorn Yutthanasirikul, Takanori Nagano, Toru Hisabori, Yukako Hihara, Yoshitaka Nishiyama
The repair of photosystem II (PSII) is particularly sensitive to oxidative stress and the inhibition of repair is associated with oxidative damage to the translational elongation system in the cyanobacterium Synechocystis sp. PCC 6803. However, the molecular mechanism of the inhibition of translational elongation remains to be clarified. In a previous study in vitro, we found that EF-Tu, a translation factor that delivers aminoacyl-tRNA to the ribosome, is inactivated by reactive oxygen species via oxidation of Cys82, a single cysteine residue...
February 8, 2018: Plant Physiology
Francesco Giansanti, David J Flavell, Francesco Angelucci, Maria Serena Fabbrini, Rodolfo Ippoliti
Plant Ribosome-inactivating proteins (RIPs) including the type I RIP Saporin have been used for the construction of Immunotoxins (ITxs) obtained via chemical conjugation of the toxic domain to whole antibodies or by generating genetic fusions to antibody fragments/targeting domains able to direct the chimeric toxin against a desired sub-population of cancer cells. The high enzymatic activity, stability and resistance to conjugation procedures and especially the possibility to express recombinant fusions in yeast, make Saporin a well-suited tool for anti-cancer therapy approaches...
February 13, 2018: Toxins
Ahmed Murtaja, Ergül Eyol, Jiang Xiaoqi, Martin R Berger, Hassan Adwan
Pancreatic ductal adenocarcinoma (PDAC) has one of the poorest prognoses of all malignancy types. To improve the survival of patients with PDAC, the development of novel anticancer agents is warranted. Riproximin (Rpx) is a newly identified plant lectin, which was isolated from Ximenia americana. The ribosome inactivating protein of type II exhibits potent anticancer activity as recently demonstrated. The rat PDAC cell line ASML was used for in vitro and in vivo studies. The antiproliferative effect of Rpx was assessed using an MTT assay...
February 2018: Oncology Letters
N Beztsinna, M B C de Matos, J Walther, C Heyder, E Hildebrandt, G Leneweit, E Mastrobattista, R J Kok
Ribosome inactivating proteins (RIPs) are highly potent cytotoxins that have potential as anticancer therapeutics. Mistletoe lectin 1 (ML1) is a heterodimeric cytotoxic protein isolated from European Mistletoe and belongs to RIP class II. The aim of this project was to systematically study ML1 cell binding, endocytosis pathway(s), subcellular processing and apoptosis activation. For this purpose, state of the art cell imaging equipment and automated image analysis algorithms were used. ML1 displayed very fast binding to sugar residues on the membrane and energy-dependent uptake in CT26 cells...
February 9, 2018: Scientific Reports
Yongxu Yang, Qi Qi, Yi Wang, Yaru Shi, Weili Yang, Yunzhu Cen, Endong Zhu, Xiaoxia Li, Di Chen, Baoli Wang
Emerging evidence suggests that cysteine-rich protein 61 (CYR61) plays a role in the differentiation and development of chondrocytes, osteoblasts, and osteoclasts; however, little is known about its role in adipogenesis. The current study indicates that the expression level of Cyr61 was altered in primary cultured marrow stromal cells and the established mesenchymal cell line, C3H10T1/2, after adipogenic treatment. Overexpressing Cyr61 repressed C3H10T1/2 and primary marrow stromal cells to differentiate into mature adipocytes...
January 18, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ran Li, Zhiqing Wang, Shu Liu, Baoping Wu, Di Zeng, Yali Zhang, Lanbo Gong, Feihong Deng, Haoxuan Zheng, Yadong Wang, Chudi Chen, Junsheng Chen, Bo Jiang
Peutz-Jeghers syndrome (PJS) is a rare hereditary disease caused by mutations in serine threonine kinase 11 (STK11) and characterized by an increased risk of developing cancer. Inactivation of STK11 has been associated with the mammalian target of rapamycin (mTOR) pathway. Hyperactivation and phosphorylation of the key downstream target genes ribosomal protein S6 kinase 1 (S6K1) and S6 promote protein synthesis and cell proliferation. To better understand the effects of STK11 dysfunction in the pathogenesis of PJS, genomic DNA samples from 21 patients with PJS from 11 unrelated families were investigated for STK11 mutations in the present study...
January 2018: Oncology Letters
Chhavi Mathur, Kory R Johnson, Brian A Tong, Pablo Miranda, Deepa Srikumar, Daniel Basilio, Ramon Latorre, Francisco Bezanilla, Miguel Holmgren
Local translation of membrane proteins in neuronal subcellular domains like soma, dendrites and axon termini is well-documented. In this study, we isolated the electrical signaling unit of an axon by dissecting giant axons from mature squids (Dosidicus gigas). Axoplasm extracted from these axons was found to contain ribosomal RNAs, ~8000 messenger RNA species, many encoding the translation machinery, membrane proteins, translocon and signal recognition particle (SRP) subunits, endomembrane-associated proteins, and unprecedented proportions of SRP RNA (~68% identical to human homolog)...
February 2, 2018: Scientific Reports
Yongchao Zhao, Mingjia Tan, Xia Liu, Xiufang Xiong, Yi Sun
RPS27L (ribosomal protein S27-like) is an evolutionarily conserved ribosomal protein and a direct p53 target. We recently reported that Rps27l disruption triggers ribosomal stress to induce p53, causing postnatal death, which can be rescued by Trp53 +/- . Whether and how Rps27l modulates radiosensitivity is unknown. Here we report that Rps27l -/- ; Trp53 +/- mice are extremely sensitive to radiation due to reduced proliferation and massive induction of apoptosis in radiation-sensitive organs. Mechanistically, the radiation sensitivity is mediated by two signaling pathways: (1) activated p53 pathway due to imbalanced Mdm2/Mdm4 levels and reduced E3 ligase activity; and (2) reduced DNA damage response due to reduced MRN/Atm signal as a result of elevated Mdm2 binding of Nbs1 to inhibit Nbs1-Atm binding and subsequent Atm activation...
February 2, 2018: Cell Death & Disease
Lei-Lei Ma, Xin Ma, Fei-Juan Kong, Jun-Jie Guo, Hong-Tao Shi, Jian-Bing Zhu, Yun-Zeng Zou, Jun-Bo Ge
Pathological cardiac hypertrophy aggravated myocardial infarction and is causally related to autophagy dysfunction and increased oxidative stress. Rapamycin is an inhibitor of serine/threonine kinase mammalian target of rapamycin (mTOR) involved in the regulation of autophagy as well as oxidative/nitrative stress. Here, we demonstrated that rapamycin ameliorates myocardial ischaemia reperfusion injury by rescuing the defective cytoprotective mechanisms in hypertrophic heart. Our results showed that chronic rapamycin treatment markedly reduced the phosphorylated mTOR and ribosomal protein S6 expression, but not Akt in both normal and aortic-banded mice...
March 2018: Journal of Cellular and Molecular Medicine
Priyanka Agrawal, Rajagopal Varada, Shivjee Sah, Souvik Bhattacharyya, Umesh Varshney
Bacteria respond to stressful growth conditions through a conserved phenomenon of 'stringent response' mediated by synthesis of stress alarmones, ppGpp or pppGpp [referred to as (p)ppGpp]. The (p)ppGpp synthesis is known to occur by ribosome associated RelA. In addition, a dual function protein SpoT (with both the synthetase and hydrolase activities) maintains (p)ppGpp homeostasis. The presence of (p)ppGpp is also known to contribute to antibiotic resistance in bacteria. Mycobacterium smegmatis possesses Arr, which inactivates rifampicin by its ADP-ribosylation...
January 8, 2018: Journal of Bacteriology
Lingling Ding, Yu Jiang, Jian Zhang, Harm-Anton Klok, Zhiyuan Zhong
The clinical translation of protein drugs that act intracellularly is limited by the absence of safe and efficient intracellular protein delivery vehicles. Here, pH-sensitive coiled-coil peptide-crosslinked hyaluronic acid nanogels (HA-cNGs) were designed and investigated for targeted intracellular protein delivery to CD44 overexpressing MCF-7 breast cancer cells. HA-cNGs were obtained with a small size of 176 nm from an equivalent mixture of hyaluronic acid conjugates with GY(EIAALEK)3GC (E3) and GY(KIAALKE)3GC (K3) peptides, respectively, at pH 7...
December 29, 2017: Biomacromolecules
Kazuei Igarashi, Takeshi Uemura, Keiko Kashiwagi
It is thought that tissue damage at advanced age is mainly caused by ROS (reactive oxygen species, O2-, H2O2, and ·OH). However, it was found that acrolein (CH2=CH-CHO) is more toxic than ROS, and is mainly produced from spermine (SPM), one of the polyamines, rather than from unsaturated fatty acids. Significant amounts of SPM are present normally as SPM-ribosome complexes, and contribute to protein synthesis. However, SPM was released from ribosomes due to the degradation of ribosomal RNA by ·OH or the binding of Ca2+ to ribosomes, and acrolein was produced from free SPM by polyamine oxidases, particularly by SPM oxidase...
December 16, 2017: Amino Acids
Reneta Gevrenova, Ventzislav Bardarov, Krum Bardarov, Laurence Voutquenne-Nazabadioko, Max Henry
INTRODUCTION: Roots of Gypsophila trichotoma Wend. (Caryophyllaceae) are rich sources of glucuronide oleanane-type triterpenoid carboxylic acid 3,28-O-bidesmosides (GOTCABs). These saponins have been reported to possess synergistic cytotoxicity in combination with type I ribosome-inactivating protein saporin. OBJECTIVE: To develop ultra high-performance liquid chromatography - electrospray ionisation/high resolution mass spectrometry (UHPLC-ESI/HRMS) acquisition strategy for the recognition of Gypsophila GOTCAB saponins...
December 4, 2017: Phytochemical Analysis: PCA
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