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Shalom Madar Einav Harel Ido Goldstein Yan Stein Ira Kogan-Sakin Iris Kamer Hilla Solomon Elya Dekel Perry Tal Naomi Goldfinger Gilgi Friedlander Varda Rotter 《PloS one》2013,8(4)
Mutations in the p53 tumor suppressor protein are highly frequent in tumors and often endow cells with tumorigenic capacities. We sought to examine a possible role for mutant p53 in the cross-talk between cancer cells and their surrounding stroma, which is a crucial factor affecting tumor outcome. Here we present a novel model which enables individual monitoring of the response of cancer cells and stromal cells (fibroblasts) to co-culturing. We found that fibroblasts elicit the interferon beta (IFNβ) pathway when in contact with cancer cells, thereby inhibiting their migration. Mutant p53 in the tumor was able to alleviate this response via SOCS1 mediated inhibition of STAT1 phosphorylation. IFNβ on the other hand, reduced mutant p53 RNA levels by restricting its RNA stabilizer, WIG1. These data underscore mutant p53 oncogenic properties in the context of the tumor microenvironment and suggest that mutant p53 positive cancer patients might benefit from IFNβ treatment. 相似文献
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Acetohydroxyacid synthase from Mycobacterium avium and its inhibition by sulfonylureas and imidazolinones 总被引:1,自引:0,他引:1
Tuberculosis (TB) remains one of the world's leading causes of death from infectious disease. It is caused by infection with Mycobacterium tuberculosis or sometimes, particularly in immune-compromised patients, Mycobacterium avium. The aim of this study was to create a tool that could be used in the search for new anti-TB drugs that inhibit branched-chain amino acid (BCAA) biosynthesis, as these are essential amino acids that are not available to a mycobacterium during growth in an infected organism. To this end, we cloned, overexpressed, purified and characterised for the first time an acetohydroxyacid synthase (AHAS), a key enzyme in the pathway to the biosynthesis of the BCAAs, from the genus Mycobacterium. Nine commercial herbicides of the sulfonylurea and imidazolinone classes were tested for their influence on this enzyme. Four of the sulfonylureas were potent inhibitors of the enzyme. The relative potency of the different inhibitors towards the M. avium enzyme was unlike their potency towards other AHASs whose inhibitor profile has been reported, emphasising the advantage of using a mycobacterial enzyme as a tool in the search for new anti-TB drugs. 相似文献
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Poornima Parameswaran Ella Sklan Courtney Wilkins Trever Burgon Melanie A. Samuel Rui Lu K. Mark Ansel Vigo Heissmeyer Shirit Einav William Jackson Tammy Doukas Suman Paranjape Charlotta Polacek Flavia Barreto dos Santos Roxana Jalili Farbod Babrzadeh Baback Gharizadeh Dirk Grimm Mark Kay Satoshi Koike Peter Sarnow Mostafa Ronaghi Shou-Wei Ding Eva Harris Marie Chow Michael S. Diamond Karla Kirkegaard Jeffrey S. Glenn Andrew Z. Fire 《PLoS pathogens》2010,6(2)
We have used multiplexed high-throughput sequencing to characterize changes in small RNA populations that occur during viral infection in animal cells. Small RNA-based mechanisms such as RNA interference (RNAi) have been shown in plant and invertebrate systems to play a key role in host responses to viral infection. Although homologs of the key RNAi effector pathways are present in mammalian cells, and can launch an RNAi-mediated degradation of experimentally targeted mRNAs, any role for such responses in mammalian host-virus interactions remains to be characterized. Six different viruses were examined in 41 experimentally susceptible and resistant host systems. We identified virus-derived small RNAs (vsRNAs) from all six viruses, with total abundance varying from “vanishingly rare” (less than 0.1% of cellular small RNA) to highly abundant (comparable to abundant micro-RNAs “miRNAs”). In addition to the appearance of vsRNAs during infection, we saw a number of specific changes in host miRNA profiles. For several infection models investigated in more detail, the RNAi and Interferon pathways modulated the abundance of vsRNAs. We also found evidence for populations of vsRNAs that exist as duplexed siRNAs with zero to three nucleotide 3′ overhangs. Using populations of cells carrying a Hepatitis C replicon, we observed strand-selective loading of siRNAs onto Argonaute complexes. These experiments define vsRNAs as one possible component of the interplay between animal viruses and their hosts. 相似文献
4.
Hepatitis C virus (HCV) is a major cause of viral hepatitis. There is no effective therapy for most patients. We have identified a nucleotide binding motif (NBM) in one of the virus's nonstructural proteins, NS4B. This structural motif binds and hydrolyzes GTP and is conserved across HCV isolates. Genetically disrupting the NBM impairs GTP binding and hydrolysis and dramatically inhibits HCV RNA replication. These results have exciting implications for the HCV life cycle and novel antiviral strategies. 相似文献
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Einav Gross Carolyn S Sevier Andrea Vala Chris A Kaiser Deborah Fass 《Nature structural biology》2002,9(1):61-67
Erv2p is an FAD-dependent sulfhydryl oxidase that can promote disulfide bond formation during protein biosynthesis in the yeast endoplasmic reticulum. The structure of Erv2p, determined by X-ray crystallography to 1.5 A resolution, reveals a helix-rich dimer with no global resemblance to other known FAD-binding proteins or thiol oxidoreductases. Two pairs of cysteine residues are required for Erv2p activity. The first (Cys-Gly-Glu-Cys) is adjacent to the isoalloxazine ring of the FAD. The second (Cys-Gly-Cys) is part of a flexible C-terminal segment that can swing into the vicinity of the first cysteine pair in the opposite subunit of the dimer and may shuttle electrons between substrate protein dithiols and the FAD-proximal disulfide. 相似文献
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Robert Manasherob Arieh Zaritsky Eitan Ben-Dov Deepak Saxena Ze'ev Barak Monica Einav 《Current microbiology》2001,43(5):355-364
The gene coding for the accessory protein P19 of Bacillus thuringiensis subsp. israelensis was expressed in Escherichia coli and its product was characterized. To investigate its putative role in δ-endotoxin crystallization as a P20-like polypeptide,
each of the two encoding genes, p20 and p19, was cloned for inducible expression coordinatively with cyt1Aa. The latter is known to kill its transgenic host. P20 but not P19 stabilized Cyt1Aa and protected the host cells from its
lethal effect. Neither GroEL nor GroES, expressed in trans, affected Cyt1Aa as did P20. The function of P20 is thus more specific than that of the chaperones, but that of P19 remains
enigmatic. The correct sequence of p19, confirmed in all five isolates of B. thuringiensis subsp. israelensis, does not explain the slow electrophoretic mobility of its 179 amino acids product.
Received: 5 March 2001 / Accepted: 3 April 2001 相似文献
10.
Ruben Girsowicz Oksana Koryachenko Chen Sherman Einav Mayzlish-Gati Tirza Doniger 《Soil & Sediment Contamination》2018,27(3):175-185
The present study evaluated the effect of crude oil contamination on a microbial community in hyper-arid soils. The Evrona Nature Reserve of Israel, situated in the Arava, was exposed twice in the last 40 years to petroleum-hydrocarbon-spill pollution. The first pollution event took place 40 years ago and was never treated, presenting a unique future time-point perspective to the second (2014) contamination event. Soil samples were collected after the second spill, and abiotic properties and bacterial diversity in the sampled soil were analyzed. The results showed that there is a significant decrease over time in the number of observed bacterial species in the contaminated samples, coupled together with bacterial species replacement toward species capable of using source oil as the sole carbon and energy source. The presence of petroleum in soil significantly changed the composition and functional diversity of a microbial community, and the Evrona Nature Reserve is still in the middle of a bioremediation process even 40 years after the crude oil contamination. 相似文献