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https://www.readbyqxmd.com/read/29777999/targeted-delivery-of-cd44s-sirna-by-scfv-overcomes-de-novo-resistance-to-cetuximab-in-triple-negative-breast-cancer
#1
Wenyan Fu, Hefen Sun, Yang Zhao, Mengting Chen, Lipeng Yang, Xueli Yang, Wei Jin
The overexpression of EGFR often occurs in TNBC, and the anti-EGFR receptor antibody cetuximab is used widely to treat metastatic cancer in the clinic. However, EGFR-targeted therapies have been developed for TNBC without clinical success. In this study, we show that impaired EGFR degradation is crucial for resistance to cetuximab, which depends on the cell surface molecule CD44. To further investigate the role of CD44 in EGFR signaling and its treatment potential, we developed a targeting fusion protein composed of an anti-EGFR scFv generated from cetuximab and truncated protamine, called Ce-tP...
May 16, 2018: Molecular Immunology
https://www.readbyqxmd.com/read/29777834/erwinia-amylovora-phage-vb_eamm_y3-represents-another-lineage-of-hairy-myoviridae
#2
Colin Buttimer, Yannick Born, Alan Lucid, Martin J Loessner, Lars Fieseler, Aidan Coffey
To date, a small number of jumbo myoviruses have been reported to possess atypical whisker-like structures along the surface of their contractile tails. Erwinia amylovora phage vB_EamM_Y3 is another example. It possesses a genome of 261,365 kbp with 333 predicted ORFs. Using a combination of BLASTP, Interproscan and HHpred, about 21% of its putative proteins could be assigned functions involved in nucleotide metabolism, DNA replication, virion structure and cell wall degradation. The phage was found to have a signal-arrest-release (SAR) endolysin (Y3_301) possessing a soluble lytic transglycosylase domain...
May 16, 2018: Research in Microbiology
https://www.readbyqxmd.com/read/29777785/psmd2-regulates-breast-cancer-cell-proliferation-and-cell-cycle-progression-by-modulating-p21-and-p27-proteasomal-degradation
#3
Yunhai Li, Jing Huang, Beilei Zeng, Dejuan Yang, Jiazheng Sun, Xuedong Yin, Mengqi Lu, Zhu Qiu, Weiyan Peng, Tingxiu Xiang, Hongzhong Li, Guosheng Ren
Alterations in the ubiquitin-proteasome system (UPS) and UPS-associated proteins have been implicated in the development of many human malignancies. In this study, we investigated the expression profiles of 797 UPS-related genes using HiSeq data from The Cancer Genome Atlas and identified that PSMD2 was markedly upregulated in breast cancer. High PSMD2 expression was significantly correlated with poor prognosis. Gene set enrichment analysis revealed that transcriptome signatures involving proliferation, cell cycle, and apoptosis were critically enriched in specimens with elevated PSMD2...
May 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29777751/evaluating-the-susceptibility-of-ago2-loaded-micrornas-to-degradation-by-nucleases-in-vitro
#4
Reyad Elbarbary, Lynne E Maquat
MicroRNAs (miRNAs) comprise a class of small non-coding RNAs that regulate the stability and/or translatability of most protein-coding transcripts. Steady-state levels of mature miRNAs can be controlled through mechanisms that influence their biogenesis and/or decay rates. Pathways that mediate mature miRNA decay are less well understood than those that mediate miRNA biogenesis. We recently described Tudor-staphylococcal/micrococcal-like nuclease (TSN)-mediated miRNA decay (TumiD) as a cellular pathway that promotes the sequence-specific endonucleolytic decay of miRNAs that harbor a CA and/or UA dinucleotide...
May 16, 2018: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/29777737/type-i-collagen-induces-mesenchymal-cell-differentiation-into-myofibroblasts-through-yap-induced-tgf-%C3%AE-1-activation
#5
Xiaoling Liu, Xinyu Long, Weiwei Liu, Yeli Zhao, Toshihiko Hayashi, Masayuki Yamato, Kazunori Mizuno, Hitomi Fujisaki, Shunji Hattori, Shin-Ichi Tashiro, Takaaki Ogura, Yuji Atsuzawa, Takashi Ikejima
In organ fibrosis, mechanical stress and transforming growth factor beta-1 (TGF-β1) promote differentiation into myofibroblast from mesenchymal cells, leading to extracellular matrix (ECM) remodeling or active synthesis, deposition or degradation of ECM components. A major component of ECM, type I collagen (col I) triple helical molecules assemble into fibrils or are denatured to gelatin without triple-helicity in remodeling. However, whether changes of ECM components in remodeling have influence on mesenchymal cell differentiation remains elusive...
May 16, 2018: Biochimie
https://www.readbyqxmd.com/read/29777712/speckle-type-poz-protein-suppresses-hepatocellular-carcinoma-cell-migration-and-invasion-via-ubiquitin-dependent-proteolysis-of-sumo1-sentrin-specific-peptidase-7
#6
Piyou Ji, Shaohua Liang, Pengtao Li, Chengrong Xie, Jie Li, Kang Zhang, Xuqing Zheng, Min Feng, Qiu Li, Hui Jiao, Xiaoqin Chi, Wenxiu Zhao, Sheng Zhang, Xiaomin Wang
Hepatocellular carcinoma (HCC) is associated with high metastatic potential and high mortality. Accumulating evidence has demonstrated that speckle-type POZ protein (SPOP) is a key adaptor molecule of ubiquitination. However, the molecular mechanism of SPOP-mediated ubiquitination in HCC metastasis remains obscure. In the present study, our results indicated that SPOP expression was significantly downregulated in HCC and was associated with tumor size, differentiation and metastasis. Cox regression model showed that low SPOP expression was a risk factor related to the prognosis of HCC patients...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777695/proteasome-mediated-protein-degradation-is-enhanced-by-fusion-ubiquitin-with-unstructured-degron
#7
Tomonao Inobe, Masayuki Tsukamoto, Miyuki Nozaki
Methods to induce proteasomal degradation of unwanted proteins are valuable in biomedical studies and thus receive increasing attention. For efficient degradation, the proteasome requires both a ubiquitin tag, which delivers substrates to the proteasome, and an unstructured region, where the proteasome engages the substrate for unfolding and degradation. We fused two degron components into a single molecule to create a fusion protein comprising ubiquitin and Rpn4-derived unstructured region. We demonstrated that the fusion protein retained its function to polyubiquitinate target proteins, thereby inducing more efficient proteasomal target degradation than wild-type ubiquitin in vitro and in cells...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29777593/degradation-of-recombinant-proteins-by-cho-host-cell-proteases-is-prevented-by-matriptase-1-knock-out
#8
Holger Laux, Sandrine Romand, Sandro Nuciforo, Christopher J Farady, Joel Tapparel, Stine Buechmann-Moeller, Benjamin Sommer, Edward J Oakeley, Ursula Bodendorf
An increasing number of non-antibody format proteins are entering the clinical development. However, one of the major hurdles for the production of non-antibody glycoproteins is host cell-related proteolytic degradation, which can drastically impact developability and timelines of pipeline projects. Chinese hamster ovary (CHO) cells are the preferred production host for recombinant therapeutic proteins. Using protease inhibitors, transcriptomics and genetic knockdowns we have identified, out of the more than 700 known proteases in rodents, Matriptase-1 as the major protease involved in degradation of recombinant proteins expressed in CHO-K1 cells...
May 19, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29777544/gingipains-disrupt-f-actin-and-cause-osteoblast-apoptosis-via-integrin-%C3%AE-1
#9
Q Qiu, F Zhang, J Wu, N Xu, M Liang
BACKGROUND AND OBJECTIVE: The aim of this study was to explore the cellular mechanisms underlying gingipain-caused changes in cell morphology and apoptosis of osteoblasts. MATERIAL AND METHODS: Human calvarial osteoblasts and mouse osteoblasts MC3T3-E1 were treated with gingipain extracts from Porphyromonas gingivalis stain W83. Apoptosis was detected with annexin V and propidium iodide flow cytometry analysis or terminal deoxynucleotidyl transferase mediated dUTP nick-end labeling staining...
May 18, 2018: Journal of Periodontal Research
https://www.readbyqxmd.com/read/29777486/physiological-and-quantitative-proteomic-analyses-unraveling-potassium-deficiency-stress-response-in-alligator-weed-alternanthera-philoxeroides-l-root
#10
Li-Qin Li, Lun Liu, Wei Zhuo, Qian Chen, Sheng Hu, Shuang Peng, Xi-Yao Wang, Yi-Fei Lu, Li-Ming Lu
Physiological and iTRAQ based proteomic analysis provided new insights into potassium deficiency stress response in alligator weed root. Alligator weed (Alternanthera philoxeroides) has a strong ability to adapt to potassium deficiency (LK) stress. Proteomic changes in response to this stress are largely unknown in alligator weed. In this study, we investigated physiological and molecular mechanisms under LK using isobaric tags for relative and absolute quantitation to characterize proteome-level changes in this plant...
May 18, 2018: Plant Molecular Biology
https://www.readbyqxmd.com/read/29777151/integrated-proteomics-genomics-metabolomics-approaches-reveal-oxalic-acid-as-pathogenicity-factor-in-tilletia-indica-inciting-karnal-bunt-disease-of-wheat
#11
Vishakha Pandey, Manoj Singh, Dinesh Pandey, Anil Kumar
Tilletia indica incites Karnal bunt (KB) disease in wheat. To date, no KB resistant wheat cultivar could be developed due to non-availability of potential biomarkers related to pathogenicity/virulence for screening of resistant wheat genotypes. The present study was carried out to compare the proteomes of T. indica highly (TiK) and low (TiP) virulent isolates. Twenty one protein spots consistently observed as up-regulated/differential in the TiK proteome were selected for identification by MALDI-TOF/TOF. Identified sequences showed homology with fungal proteins playing essential role in plant infection and pathogen survival, including stress response, adhesion, fungal penetration, invasion, colonization, degradation of host cell wall, signal transduction pathway...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29777017/old-enzymes-versus-new-herbicides
#12
Tamara L Hendrickson
The introduction of manmade chemicals, including the herbicide atrazine, into the environment has led to the emergence of microorganisms with new biodegradation pathways. Esquirol et al. demonstrate that the AtzE enzyme catalyzes a central step in atrazine degradation and that expression of AtzE requires coexpression of the small protein AtzG. Remarkably, AtzG and AtzE appear to have evolved from GatC and GatA, components of an ancient enzyme involved in indirect tRNA aminoacylation, providing an elegant demonstration of metabolic repurposing...
May 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29776748/conserved-degradation-of-orthologous-rlcks-regulates-immune-homeostasis
#13
Jacqueline Monaghan
Arabidopsis (Arabidopsis thaliana) AtBIK1 and rice (Oryza sativa) OsRLCK176 are orthologous receptor-like cytoplasmic kinases involved in immune signaling. Recent studies indicate that proteasomal turnover of these kinases is regulated by orthologous Ca2+ -dependent protein kinases AtCPK28 and OsCPK4, revealing conserved interplay between phosphorylation and ubiquitination in immune homeostasis.
May 15, 2018: Trends in Plant Science
https://www.readbyqxmd.com/read/29776407/comparative-genomics-of-the-miniature-wasp-and-pest-control-agent-trichogramma-pretiosum
#14
Amelia R I Lindsey, Yogeshwar D Kelkar, Xin Wu, Dan Sun, Ellen O Martinson, Zhichao Yan, Paul F Rugman-Jones, Daniel S T Hughes, Shwetha C Murali, Jiaxin Qu, Shannon Dugan, Sandra L Lee, Hsu Chao, Huyen Dinh, Yi Han, Harsha Vardhan Doddapaneni, Kim C Worley, Donna M Muzny, Gongyin Ye, Richard A Gibbs, Stephen Richards, Soojin V Yi, Richard Stouthamer, John H Werren
BACKGROUND: Trichogrammatids are minute parasitoid wasps that develop within other insect eggs. They are less than half a millimeter long, smaller than some protozoans. The Trichogrammatidae are one of the earliest branching families of Chalcidoidea: a diverse superfamily of approximately half a million species of parasitoid wasps, proposed to have evolved from a miniaturized ancestor. Trichogramma are frequently used in agriculture, released as biological control agents against major moth and butterfly pests...
May 18, 2018: BMC Biology
https://www.readbyqxmd.com/read/29776055/optimal-methylation-noise-for-best-chemotactic-performance-of-e-coli
#15
Subrata Dev, Sakuntala Chatterjee
In response to a concentration gradient of chemoattractant, E. coli bacterium modulates the rotational bias of flagellar motors which control its run-and-tumble motion, to migrate towards regions of high chemoattractant concentration. Presence of stochastic noise in the biochemical pathway of the cell has important consequences on the switching mechanism of motor bias, which in turn affects the runs and tumbles of the cell in a significant way. We model the intracellular reaction network in terms of coupled time evolution of three stochastic variables-kinase activity, methylation level, and CheY-P protein level-and study the effect of methylation noise on the chemotactic performance of the cell...
March 2018: Physical Review. E
https://www.readbyqxmd.com/read/29775942/toxicological-effects-on-earthworms-eisenia-fetida-exposed-to-sub-lethal-concentrations-of-bde-47-and-bde-209-from-a-metabolic-point
#16
Ruoyu Liang, Juan Chen, Yajuan Shi, Yonglong Lu, Suriyanarayanan Sarvajayakesavalu, Xiangbo Xu, Xiaoqi Zheng, Kifayatullah Khan, Chao Su
Earthworms improve the soil fertility and they are also sensitive to soil contaminants. Earthworms (Eisenia fetida), standard reference species, were usually chosen to culture and handle for toxicity tests. Metabolic responses in earthworms exposed to 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209) were inhibitory and interfered with basal metabolism. In this study, 1 H-NMR based metabolomics was used to identify sensitive biomarkers and explore metabolic responses of earthworms under sub-lethal BDE-47 and BDE-209 concentrations for 14 days...
May 15, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29775763/photoreceptor-mediated-regulation-of-the-cop1-spa-e3-ubiquitin-ligase
#17
REVIEW
Roman Podolec, Roman Ulm
Plants have evolved specific photoreceptors that capture informational cues from sunlight. The phytochrome, cryptochrome, and UVR8 photoreceptors perceive red/far-red, blue/UV-A, and UV-B light, respectively, and control overlapping photomorphogenic responses important for plant growth and development. A major repressor of such photomorphogenic responses is the E3 ubiquitin ligase formed by CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) and SUPPRESSOR OF PHYA-105 (SPA) proteins, which acts by regulating the stability of photomorphogenesis-promoting transcription factors...
May 15, 2018: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/29775750/the-effects-of-capn1-gene-inactivation-on-the-differential-expression-of-genes-in-skeletal-muscle
#18
William T Olive, Brittney N Keel, Amanda K Lindholm-Perry, Justyna Horodyska, Andrew P Foote
Protein turnover is required for muscle growth and regeneration and several proteolytic enzymes, including the calpains, degrade myofibrillar proteins during this process. In a previous experiment, phenotypic differences were observed between μ-calpain knockout (KO) and wild type (WT) mice, including nutrient accretion and fiber type differences. These changes were particularly evident as the animals aged. Thus, we utilized 18 mice (9 KO and 9 WT) to compare transcript abundance to identify differentially expressed genes (DEGs) at 52 wk of age...
May 15, 2018: Gene
https://www.readbyqxmd.com/read/29775708/gelatin-alginate-coacervates-for-circumventing-proteolysis-and-probing-intermolecular-interactions-by-spr
#19
Hui-Chong Lau, Seonghee Jeong, Aeri Kim
Complex coacervates based on natural biopolymers have been explored as a protein delivery system to provide controlled release of loaded protein and circumvent its proteolytic degradation in chronic wounds. The coacervates composed of gelatin A (GA) and sodium alginate (SA) were optimized with respect to turbidity, size, zeta potential, and polydispersity index. Bovine serum albumin (BSA), a model protein, was effectively encapsulated in the coacervates, resulting in protection from trypsin digestion and controlled release...
May 15, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29775704/alkaline-active-cyanide-dihydratase-of-flavobacterium-indicum-mtcc-6936-growth-optimization-purification-characterization-and-in-silico-analysis
#20
Virender Kumar, Vijay Kumar, Tek Chand Bhalla
The present work explores a rare cyanide dihydratase of Flavobacterium indicum MTCC 6936 for its potential of cyanide degradation. The enzyme is purified to 12 fold with a yield of 76%. SDS and native-PAGE analysis revealed that enzyme was monomer of 40 kDa size. The enzyme works well in mesophilic range at wide array of pH. The thermostability profile of cyanide dihydratase revealed that the enzyme is quite stable at 30 °C and 35 °C with half-life of 6 h 30 min and 5 h respectively. Km and Vmax for cyanide dihydratase of F...
May 15, 2018: International Journal of Biological Macromolecules
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