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81.
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Alexander Bobbs Katrina Gellerman William Morgan Hallas Stancy Joseph Chao Yang Jeffrey Kurkewich Karen D. Cowden Dahl 《PloS one》2015,10(6)
The DNA-binding protein AT-Rich Interactive Domain 3B (ARID3B) is elevated in ovarian cancer and increases tumor growth in a xenograft model of ovarian cancer. However, relatively little is known about ARID3B''s function. In this study we perform the first genome wide screen for ARID3B direct target genes and ARID3B regulated pathways. We identified and confirmed numerous ARID3B target genes by chromatin immunoprecipitation (ChIP) followed by microarray and quantitative RT-PCR. Using motif-finding algorithms, we characterized a binding site for ARID3B, which is similar to the previously known site for the ARID3B paralogue ARID3A. Functionality of this predicted site was demonstrated by ChIP analysis. We next demonstrated that ARID3B induces expression of its targets in ovarian cancer cell lines. We validated that ARID3B binds to an epidermal growth factor receptor (EGFR) enhancer and increases mRNA expression. ARID3B also binds to the promoter of Wnt5A and its receptor FZD5. FZD5 is highly expressed in ovarian cancer cell lines, and is upregulated by exogenous ARID3B. Both ARID3B and FZD5 expression increase adhesion to extracellular matrix (ECM) components including collagen IV, fibronectin and vitronectin. ARID3B-increased adhesion to collagens II and IV require FZD5. This study directly demonstrates that ARID3B binds target genes in a sequence-specific manner, resulting in increased gene expression. Furthermore, our data indicate that ARID3B regulation of direct target genes in the Wnt pathway promotes adhesion of ovarian cancer cells. 相似文献
84.
Lakhe-Reddy S Khan S Konieczkowski M Jarad G Wu KL Reichardt LF Takai Y Bruggeman LA Wang B Sedor JR Schelling JR 《The Journal of biological chemistry》2006,281(28):19688-19699
Alpha(v)beta8 integrin expression is restricted primarily to kidney, brain, and placenta. Targeted alpha(v) or beta8 deletion is embryonic lethal due to defective placenta and brain angiogenesis, precluding investigation of kidney alpha(v)beta8 function. We find that kidney beta8 is localized to glomerular mesangial cells, and expression is decreased in mouse models of glomerulosclerosis, suggesting that beta8 regulates normal mesangial cell differentiation. To interrogate beta8 signaling pathways, yeast two-hybrid and co-precipitation studies demonstrated beta8 interaction with Rho guanine nucleotide dissociation inhibitor-1 (GDI). Selective beta8 stimulation enhanced beta8-GDI interaction as well as Rac1 (but not RhoA) activation and lamellipodia formation. Mesangial cells from itgb8-/- mice backcrossed to a genetic background that permitted survival, or gdi-/- mice, which develop glomerulosclerosis, demonstrated RhoA (but not Rac1) activity and alpha-smooth muscle actin assembly, which characterizes mesangial cell myofibroblast transformation in renal disease. To determine whether Rac1 directly modulates RhoA-associated myofibroblast differentiation, mesangial cells were transduced with inhibitory Rac peptide fused to human immunodeficiency virus-Tat, resulting in enhanced alpha-smooth muscle actin organization. We conclude that the beta8 cytosolic tail in mesangial cells organizes a signaling complex that culminates in Rac1 activation to mediate wild-type differentiation, whereas decreased beta8 activation shifts mesangial cells toward a RhoA-dependent myofibroblast phenotype. 相似文献
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86.
Sean Michael Halloran Jeffrey Adelberg 《In vitro cellular & developmental biology. Plant》2011,47(2):257-273
Tissue culture medium is often overlooked as a factor in plant biotechnology. Most work uses Murashige and Skoog (MS; Physiol Plant in 15:473–497, 1962) inorganic medium formulation, which is not likely optimal for many of the plant systems where it is used. This current study of macronutrient factors simultaneously altered media volume and amount of tissue (plants per vessel), sucrose, nitrogen (as NO3− and NH4+ ions), and K+ in a d-optimal design space with only 55 experimental units (including five true replicates). Meso- and micro-nutrient concentrations were lowered (5% of MS) to determine which elements were most critical to plantlet quality. Plantlet quality was quantified by multiplication in the laboratory and survival and growth in the greenhouse. Plantlets grown at the lowest plant density, the lowest macronutrient concentration (20 mM), and equi-molar proportions of NH4+/K+ resulted in the best multiplication ratio and 100% greenhouse survival. Multiplication ratio in vitro and survival in the greenhouse were well correlated with one another. Laboratory dry mass, media use, sucrose use, and the uptake of the macronutrients NO3−, NH4+, and K+ were not well correlated with plantlet quality. Plantlets with the greatest uptake of P, Ca, Mg, and Mn had the best multiplication in the laboratory and on subsequent transfer, acclimatized and grew fastest in the greenhouse. Phosphorus was shown to be most depleted in media. This work demonstrates a platform to simultaneously optimize several nutritive components of tissue culture media to produce plantlets that perform well in both laboratory and greenhouse environments. Plant quality was related with factors outside the macronutrient design, and this platform indicated where to expand the experimental space. Fixed, flat-screen presentations revealed less of the response surface than interactive profiles driven by the reader. 相似文献
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88.
Ryan Wilcox Bryan E Welm Jeffrey T Chang Evan Johnson Avrum Spira Stefanie S Jeffrey Andrea H Bild 《Molecular systems biology》2011,7(1)
Identifying the best drug for each cancer patient requires an efficient individualized strategy. We present MATCH (M erging genomic and pharmacologic A nalyses for T herapy CH oice), an approach using public genomic resources and drug testing of fresh tumor samples to link drugs to patients. Valproic acid (VPA) is highlighted as a proof‐of‐principle. In order to predict specific tumor types with high probability of drug sensitivity, we create drug response signatures using publically available gene expression data and assess sensitivity in a data set of >40 cancer types. Next, we evaluate drug sensitivity in matched tumor and normal tissue and exclude cancer types that are no more sensitive than normal tissue. From these analyses, breast tumors are predicted to be sensitive to VPA. A meta‐analysis across breast cancer data sets shows that aggressive subtypes are most likely to be sensitive to VPA, but all subtypes have sensitive tumors. MATCH predictions correlate significantly with growth inhibition in cancer cell lines and three‐dimensional cultures of fresh tumor samples. MATCH accurately predicts reduction in tumor growth rate following VPA treatment in patient tumor xenografts. MATCH uses genomic analysis with in vitro testing of patient tumors to select optimal drug regimens before clinical trial initiation. 相似文献
89.
Tsunenori Nozawa Jeffrey T. Trost Taisei Fukada Masahiro Hatano James D. McManus Robert E. Blankenship 《BBA》1987,894(3):468-476
Reaction centers were purified from the thermophilic purple sulfur photosynthetic bacterium Chromatium tepidum. The reaction center consists of four polypeptides L, M, H and C, whose apparent molecular masses were determined to be 25, 30, 34 and 44 kDa, respectively, by polyacrylamide gel electrophoresis. The heaviest peptide corresponds to tightly bound cytochrome. The tightly bound cytochrome c contains two types of heme, high-potential c-556 and low-potential c-553. The low-potential heme is able to be photooxidized at 77 K. The reaction center exhibits laser-flash-induced absorption changes and circular dichroism spectra similar to those observed in other purple photosynthetic bacteria. Whole cells contain both ubiquinone and menaquinone. Reaction centers contain only a single active quinone; chemical analysis showed this to be menaquinone. Reaction center complexes without the tightly bound cytochrome were also prepared. The near-infrared pigment absorption bands are red-shifted in reaction centers with cytochrome compared to those without cytochrome. 相似文献
90.
Redzic JS Armstrong GS Isern NG Jones DN Kieft JS Eisenmesser EZ 《Journal of molecular biology》2011,411(1):68-82
CD147 is a type I transmembrane protein that is involved in inflammatory diseases, cancer progression, and multiple human pathogens utilize CD147 for efficient infection. CD147 expression is so high in several cancers that it is now used as a prognostic marker. The two primary isoforms of CD147 that are related to cancer progression have been identified, differing in their number of immunoglobulin (Ig)-like domains. These include CD147 Ig1-Ig2, which is ubiquitously expressed in most tissues, and CD147 Ig0-Ig1-Ig2, which is retinal specific and implicated in retinoblastoma. However, little is known in regard to the retinal specific CD147 Ig0 domain despite its potential role in retinoblastoma. We present the first crystal structure of the human CD147 Ig0 domain and show that the CD147 Ig0 domain is a crystallographic dimer with an I-type domain structure, which maintained in solution. Furthermore, we have utilized our structural data together with mutagenesis to probe the biological activity of CD147-containing proteins, both with and without the CD147 Ig0 domain, within several model cell lines. Our findings reveal that the CD147 Ig0 domain is a potent stimulator of interleukin-6 and suggest that the CD147 Ig0 domain has its own receptor distinct from that of the other CD147 Ig-like domains, CD147 Ig1-Ig2. Finally, we show that the CD147 Ig0 dimer is the functional unit required for activity and can be disrupted by a single point mutation. 相似文献