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ribosome inactivating protein

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...
April 17, 2017: Acta Pharmacologica Sinica
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
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
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
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
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
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
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
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
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
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
Bhavana Sant, P V Lakshmana Rao, D P Nagar, S C Pant, A S B Bhasker
Abrin is a potent plant toxin analogous to ricin that is derived from the seeds of Abrus precatorius plant. It belongs to the family of type II ribosome-inactivating proteins and causes cell death by irreversibly inactivating ribosomes through site-specific depurination. In this study we examined the in vivo nephrotoxicity potential of abrin toxin in terms of oxidative stress, inflammation, histopathological changes and biomarkers of kidney injury. Animals were exposed to 0.5 and 1.0 LD50 dose of abrin by intraperitoneal route and observed for 1, 3, and 7 day post-toxin exposure...
March 10, 2017: Toxicon: Official Journal of the International Society on Toxinology
Ram Ajore, David Raiser, Marie McConkey, Magnus Jöud, Bernd Boidol, Brenton Mar, Gordon Saksena, David M Weinstock, Scott Armstrong, Steven R Ellis, Benjamin L Ebert, Björn Nilsson
Heterozygous inactivating mutations in ribosomal protein genes (RPGs) are associated with hematopoietic and developmental abnormalities, activation of p53, and altered risk of cancer in humans and model organisms. Here we performed a large-scale analysis of cancer genome data to examine the frequency and selective pressure of RPG lesions across human cancers. We found that hemizygous RPG deletions are common, occurring in about 43% of 10,744 cancer specimens and cell lines. Consistent with p53-dependent negative selection, such lesions are underrepresented in TP53-intact tumors (P ≪ 10(-10)), and shRNA-mediated knockdown of RPGs activated p53 in TP53-wild-type cells...
April 2017: EMBO Molecular Medicine
Tomoko Kawamata, Tetsuro Horie, Miou Matsunami, Michiko Sasaki, Yoshinori Ohsumi
Zinc is an essential nutrient for all forms of life. Within cells, most zinc is bound to protein. Because zinc serves as a catalytic or structural cofactor for many proteins, cells must maintain zinc homeostasis under severely zinc-deficient conditions. In yeast, the transcription factor Zap1 controls the expression of genes required for uptake and mobilization of zinc, but to date the fate of existing zinc-binding proteins under zinc starvation remains poorly understood. Autophagy is an evolutionarily conserved cellular degradation/recycling process in which cytoplasmic proteins and organelles are sequestered for degradation in the vacuole/lysosome...
March 6, 2017: Journal of Biological Chemistry
Yongzhuo Huang, Victor C Yang, Feng Li, Meong Cheol Shin, Huiyuan Wang, Kyoung Ah Min, Meng Zhang, Yingzhi Chen
Ribosome-inactivating proteins (RIPs) are wildly found in multiple species of plants, bacteria and fungi. As a special family of protein toxins, RIPs can inhibit protein synthesis and induce cell death via inactivating ribosome in eukaryotic cells. Thus, RIPs have been applied for anti-tumor therapy in the past two decades. However, because of poor cell permeability, nonselective mode of action for tumor cells, poor pharmacokinetic profiles and immunogenicity, their clinical application has been severely constrained...
March 1, 2017: Current Drug Targets
Els J M Van Damme
The family of ribosome-inactivating proteins (RIPs) groups all enzymes (EC. with a so-called RIP domain which comprises N-glycosidase activity and enables these proteins to catalytically inactivate ribosomes.[...].
February 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Laura Fancello, Kim R Kampen, Isabel J F Hofman, Jelle Verbeeck, Kim De Keersmaecker
For many years, defects in the ribosome have been associated to cancer. Recently, somatic mutations and deletions affecting ribosomal protein genes were identified in a few leukemias and solid tumor types. However, systematic analysis of all 81 known ribosomal protein genes across cancer types is lacking. We screened mutation and copy number data of respectively 4926 and 7322 samples from 16 cancer types and identified six altered genes (RPL5, RPL11, RPL23A, RPS5, RPS20 and RPSA). RPL5 was located at a significant peak of heterozygous deletion or mutated in 11% of glioblastoma, 28% of melanoma and 34% of breast cancer samples...
February 28, 2017: Oncotarget
Andrea Bolognesi, Massimo Bortolotti, Maria Giulia Battelli, Letizia Polito
The enzymes called ribosome-inactivating proteins (RIPs) that are able to depurinate  nucleic acids and arrest vital cellular functions, including protein synthesis, are still a frontline  research field, mostly because of their promising medical applications. The contributions of Stirpe  to the development of these studies has been one of the most relevant. After a short biographical  introduction, an overview is offered of the main results obtained by his investigations during last  55 years on his main research lines: hyperuricaemia, xanthine oxidoreductase and RIPs...
January 27, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Huijie Fan, Jing Li, Yongxu Jia, Jingjing Wu, Long Yuan, Mingjun Li, Jiangqi Wei, Benling Xu
Ribosomal protein L34 (RPL34) belongs to the L34E family of ribosomal proteins and contains a zinc finger motif. Aberrant expression of RPL34 has been reported in several human malignancies. However, the precise role and potential underlying mechanisms of RPL34 in human esophageal cancer remain largely unknown. Thus, the objective of this study was to investigate the role of RPL34 in esophageal cancer progression. Our results showed that the expression of RPL34 at both mRNA and protein levels was frequently up-regulated in esophageal cancer cell lines...
January 20, 2017: Oncology Research
Natalya N Degtyareva, Changjun Gong, Sandra Story, Nathanael S Levinson, Adegboyega K Oyelere, Keith D Green, Sylvie Garneau-Tsodikova, Dev P Arya
The antibacterial effects of aminoglycosides are based on their association with the A-site of bacterial rRNA and interference with the translational process in the bacterial cell, causing cell death. The clinical use of aminoglycosides is complicated by resistance and side effects, some of which arise from their interactions with the human mitochondrial 12S rRNA and its deafness-associated mutations, C1494U and A1555G. We report a rapid assay that allows screening of aminoglycoside compounds to these classes of rRNAs...
February 17, 2017: ACS Infectious Diseases
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