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5101
[ "After", "treatment", "of", "APL", "cells", "with", "AM580", "either", "alone", "or", "in", "combination", "with", "granulocyte", "colony-stimulating", "factor", "(", "G-CSF", ")", ",", "the", "compound", "induces", "granulocytic", "maturation", ",", "as", "assessed", "by", "determination", "of", "the", "levels", "of", "leukocyte", "alkaline", "phosphatase", ",", "CD11b", ",", "CD33", ",", "and", "G-CSF", "receptor", "mRNA", ",", "at", "concentrations", "that", "are", "10-", "to", "100-fold", "lower", "than", "those", "of", "ATRA", "necessary", "to", "produce", "similar", "effects", "." ]
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5102
[ "By", "contrast", ",", "AM580", "is", "not", "effective", "as", "ATRA", "in", "modulating", "the", "expression", "of", "these", "differentiation", "markers", "in", "the", "HL-60", "cell", "line", "and", "in", "freshly", "isolated", "granulocytes", "obtained", "from", "the", "peripheral", "blood", "of", "chronic", "myelogenous", "leukemia", "patients", "during", "the", "stable", "phase", "of", "the", "disease", "." ]
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5103
[ "In", "NB4", "cells", ",", "two", "other", "synthetic", "nonselective", "RAR", "ligands", "are", "capable", "of", "inducing", "LAP", "as", "much", "as", "AM580", ",", "whereas", "RAR", "beta-", "or", "RAR", "gamma-specific", "ligands", "are", "totally", "ineffective", "." ]
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5104
[ "These", "results", "show", "that", "AM580", "is", "more", "powerful", "than", "ATRA", "in", "modulating", "the", "expression", "of", "differentiation", "antigens", "only", "in", "cells", "in", "which", "PML-RAR", "is", "present", "." ]
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5105
[ "Binding", "experiments", ",", "using", "COS-7", "cells", "transiently", "transfected", "with", "PML-RAR", "and", "the", "normal", "RAR", "alpha", ",", "show", "that", "AM580", "has", "a", "lower", "affinity", "than", "ATRA", "for", "both", "receptors", "." ]
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5106
[ "However", ",", "in", "the", "presence", "of", "PML-RAR", ",", "the", "synthetic", "retinoid", "is", "a", "much", "better", "transactivator", "of", "retinoic", "acid-responsive", "element-containing", "promoters", "than", "the", "natural", "retinoid", ",", "whereas", ",", "in", "the", "presence", "of", "RAR", "alpha", ",", "AM580", "and", "ATRA", "have", "similar", "activity", "." ]
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5107
[ "This", "may", "explain", "the", "strong", "cyto-differentiating", "potential", "of", "AM580", "in", "PML-RAR-containing", "leukemic", "cells", "." ]
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5108
[ "Inhibition", "of", "vitamin", "D", "receptor-retinoid", "X", "receptor-vitamin", "D", "response", "element", "complex", "formation", "by", "nuclear", "extracts", "of", "vitamin", "D-resistant", "New", "World", "primate", "cells", "." ]
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5109
[ "Most", "New", "World", "primate", "(", "NWP", ")", "genera", "evolved", "to", "require", "high", "circulating", "levels", "of", "steroid", "hormones", "and", "vitamin", "D", "." ]
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5110
[ "We", "hypothesized", "that", "an", "intracellular", "vitamin", "D", "binding", "protein", "(", "IDBP", ")", ",", "present", "in", "both", "nuclear", "and", "cytoplasmic", "fractions", "of", "NWP", "cells", ",", "or", "another", "protein", "(", "s", ")", "may", "cause", "or", "contribute", "to", "the", "steroid", "hormone-resistant", "state", "in", "NWP", "by", "disruption", "of", "the", "receptor", "dimerization", "process", "and/or", "by", "interference", "of", "receptor", "complex", "binding", "to", "the", "consensus", "response", "elements", "present", "in", "the", "enhancer", "regions", "of", "steroid-responsive", "genes", "." ]
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5111
[ "We", "employed", "electromobility", "shift", "assay", "(", "EMSA", ")", "to", "screen", "for", "the", "presence", "of", "proteins", "capable", "of", "binding", "to", "the", "vitamin", "D", "response", "element", "(", "VDRE", ")", "." ]
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5112
[ "Nuclear", "and", "post-nuclear", "extracts", "were", "prepared", "from", "two", "B-lymphoblastoid", "cell", "lines", "known", "to", "be", "representative", "of", "the", "vitamin", "D-resistant", "and", "wild", "type", "phenotypes", ",", "respectively", "." ]
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5113
[ "The", "extracts", "were", "compared", "for", "their", "ability", "to", "retard", "the", "migration", "of", "radiolabeled", "double", "stranded", "oligomers", "representative", "of", "the", "VDREs", "of", "the", "human", "osteocalcin", "and", "the", "mouse", "osteopontin", "gene", "promoters", "." ]
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5114
[ "A", "specific", ",", "retarded", "band", "containing", "VDR-RXR", "was", "identified", "when", "wild", "type", "cell", "but", "not", "when", "vitamin", "D-resistant", "cell", "nuclear", "extract", "was", "used", "in", "the", "binding", "reaction", "with", "either", "probe", "." ]
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5115
[ "In", "addition", ",", "vitamin", "D-resistant", "cell", "nuclear", "extract", "contained", "a", "protein", "(", "s", ")", "which", "was", "bound", "specifically", "to", "the", "VDRE", "and", "was", "capable", "of", "completely", "inhibiting", "VDR-RXR-VDRE", "complex", "formation", ";", "these", "effects", "were", "not", "demonstrated", "with", "nuclear", "extract", "from", "the", "wild", "type", "cell", "line", "or", "with", "the", "post-nuclear", "extract", "of", "the", "vitamin", "D-resistant", "cell", "line", "." ]
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5116
[ "We", "conclude", "that", "a", "VDRE-binding", "protein", "(", "s", ")", ",", "distinct", "from", "IDBP", "and", "present", "in", "nuclear", "extract", "of", "cells", "from", "a", "prototypical", "vitamin", "D-resistant", "NWP", ",", "is", "capable", "of", "inhibiting", "normal", "VDR-RXR", "heterodimer", "binding", "to", "the", "VDRE", "." ]
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5117
[ "BCL-6", "expression", "during", "B-cell", "activation", "." ]
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5118
[ "Translocations", "involving", "the", "BCL-6", "gene", "are", "common", "in", "the", "diffuse", "large", "cell", "subtype", "of", "non-Hodgkin", "'s", "lymphoma", "." ]
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5119
[ "Invariably", ",", "the", "BCL-6", "coding", "region", "is", "intact", ",", "but", "its", "5", "'", "untranslated", "region", "is", "replaced", "with", "sequences", "from", "the", "translocation", "partner", "." ]
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5120
[ "The", "present", "study", "shows", "that", "BCL-6", "expression", "is", "regulated", "in", "lymphocytes", "during", "mitogenic", "stimulation", "." ]
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5121
[ "Resting", "B", "and", "T", "lymphocytes", "contain", "high", "levels", "of", "BCL-6", "mRNA", "." ]
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5122
[ "Stimulation", "of", "mouse", "B", "cells", "with", "anti-IgM", "or", "IgD", "antibodies", ",", "bacterial", "lipopolysaccharide", ",", "phorbol", "12-myristate", "13-acetate", "plus", "ionomycin", ",", "or", "CD40", "ligand", "led", "to", "a", "five-fold", "to", "35-fold", "decrease", "in", "BCL-6", "mRNA", "levels", "." ]
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5123
[ "Similar", "downregulation", "of", "BCL-6", "mRNA", "was", "seen", "in", "human", "B", "cells", "stimulated", "with", "Staphylococcus", "aureus", "plus", "interleukin-2", "or", "anti-IgM", "antibodies", "and", "in", "human", "T", "lymphocytes", "stimulated", "with", "phytohemagglutinin", "." ]
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5124
[ "BCL-6", "mRNA", "levels", "began", "to", "decrease", "8", "to", "16", "hours", "after", "stimulation", ",", "before", "cells", "entered", "S", "phase", "." ]
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5125
[ "Although", "polyclonal", "activation", "of", "B", "cells", "in", "vitro", "invariably", "decreased", "BCL-6", "MRNA", "expression", ",", "activated", "B", "cells", "from", "human", "germinal", "centers", "expressed", "BCL-6", "mRNA", "at", "levels", "comparable", "to", "the", "levels", "in", "resting", "B", "cells", "." ]
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5126
[ "Despite", "these", "similar", "mRNA", "levels", ",", "BCL-6", "protein", "expression", "was", "threefold", "to", "34-fold", "higher", "in", "germinal", "center", "B", "cells", "than", "in", "resting", "B", "cells", ",", "suggesting", "that", "BCL-6", "protein", "levels", "are", "controlled", "by", "translational", "or", "posttranslational", "mechanisms", "." ]
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5127
[ "These", "observations", "suggest", "that", "the", "germinal", "center", "reaction", "provides", "unique", "activation", "signals", "to", "B", "cells", "that", "allow", "for", "continued", ",", "high-level", "BCL-6", "expression", "." ]
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5128
[ "DNA-binding", "phosphoproteins", "induced", "after", "T", "cell", "activation", ":", "effects", "of", "cyclosporin", "A", "." ]
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5129
[ "To", "define", "novel", "proteins", "involved", "in", "the", "early", "transcriptional", "response", "during", "the", "activation", "of", "human", "T", "lymphocytes", ",", "we", "used", "a", "high-resolution", ",", "two-dimensional", "gel", "electrophoresis", "system", "to", "identify", "nuclear", ",", "deoxyribonucleic", "acid", "(", "DNA", ")", "binding", "proteins", "exhibiting", "rapid", "changes", "in", "phosphorylation", "following", "cell", "stimulation", "." ]
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5130
[ "We", "identified", "18", "nuclear", "proteins", "whose", "phosphorylation", "level", "changed", "more", "than", "5-fold", "upon", "activation", "." ]
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5131
[ "Of", "these", ",", "11", "were", "found", "to", "possess", "DNA-binding", "properties", "." ]
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5132
[ "The", "11", "phosphoproteins", "with", "DNA-binding", "activity", ",", "along", "with", "4", "others", ",", "were", "analyzed", "further", "." ]
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5133
[ "Phosphoamino", "acid", "analysis", "revealed", "several", "sets", "of", "proteins", "with", "different", "phosphorylated", "residues", "Kinetic", "analysis", "of", "the", "phosphorylation", "of", "the", "selected", "proteins", "was", "performed", "and", "revealed", "a", "complex", "group", "of", "transient", "and", "sustained", "responses", "to", "cell", "activation", "." ]
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5134
[ "Finally", ",", "the", "activation-induced", "changes", "in", "one", "set", "of", "phosphoproteins", "were", "dramatically", "inhibited", "by", "cyclosporin", "A", "." ]
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5135
[ "We", "suggest", "that", "these", "phosphoproteins", "may", "be", "directly", "involved", "in", "regulating", "the", "transcriptional", "response", "to", "cellular", "activation", "by", "external", "stimuli", "." ]
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5136
[ "Inactivation", "of", "IkappaBbeta", "by", "the", "tax", "protein", "of", "human", "T-cell", "leukemia", "virus", "type", "1", ":", "a", "potential", "mechanism", "for", "constitutive", "induction", "of", "NF-kappaB", "." ]
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5137
[ "In", "resting", "T", "lymphocytes", ",", "the", "transcription", "factor", "NF-kappaB", "is", "sequestered", "in", "the", "cytoplasm", "via", "interactions", "with", "members", "of", "the", "I", "kappa", "B", "family", "of", "inhibitors", ",", "including", "IkappaBalpha", "and", "IkappaBbeta", "." ]
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5138
[ "During", "normal", "T-cell", "activation", ",", "IkappaBalpha", "is", "rapidly", "phosphorylated", ",", "ubiquitinated", ",", "and", "degraded", "by", "the", "26S", "proteasome", ",", "thus", "permitting", "the", "release", "of", "functional", "NF-kappaB", "." ]
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5139
[ "In", "contrast", "to", "its", "transient", "pattern", "of", "nuclear", "induction", "during", "an", "immune", "response", ",", "NF-kappaB", "is", "constitutively", "activated", "in", "cells", "expressing", "the", "Tax", "transforming", "protein", "of", "human", "T-cell", "leukemia", "virus", "type", "I", "(", "HTLV-1", ")", "." ]
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5140
[ "Recent", "studies", "indicate", "that", "HTLV-1", "Tax", "targets", "IkappaBalpha", "to", "the", "ubiquitin-proteasome", "pathway", "." ]
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5141
[ "However", ",", "it", "remains", "unclear", "how", "this", "viral", "protein", "induces", "a", "persistent", "rather", "than", "transient", "NF-kappaB", "response", "." ]
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5142
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5143
[ "Like", "IkappaBalpha", ",", "Tax", "-mediated", "breakdown", "of", "IkappaBbeta", "in", "transfected", "T", "lymphocytes", "is", "blocked", "either", "by", "cell-permeable", "proteasome", "inhibitors", "or", "by", "mutation", "Of", "IkappaBbeta", "at", "two", "serine", "residues", "present", "within", "its", "N-terminal", "region", "." ]
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5144
[ "Despite", "the", "dual", "specificity", "of", "HTLV-1", "Tax", "for", "IkappaBalpha", "and", "IkappaBbeta", "at", "the", "protein", "level", ",", "Tax", "selectively", "stimulates", "NF-kappaB", "-directed", "transcription", "of", "the", "IkappaBalpha", "gene", "." ]
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5145
[ "Consequently", ",", "IkappaBbeta", "protein", "expression", "is", "chronically", "downregulated", "in", "HTLV-1-infected", "T", "lymphocytes", "." ]
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5146
[ "These", "findings", "with", "IkappaBbeta", "provide", "a", "potential", "mechanism", "for", "the", "constitutive", "activation", "of", "NF-kappaB", "in", "Tax-expressing", "cells", "." ]
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5147
[ "The", "role", "of", "p16", "in", "the", "E2F-dependent", "thymidine", "kinase", "regulation", "." ]
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5148
[ "The", "role", "of", "alterations", "of", "the", "MTS1", "tumor", "suppressor", "gene", "on", "chromosome", "9p21", ",", "which", "encodes", "p16", ",", "the", "inhibitor", "of", "cyclin-dependent-kinase-4", "and", "6", ",", "in", "tumorigenesis", "is", "not", "yet", "clear", "." ]
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5149
[ "Phosphorylation", "of", "the", "retinoblastoma", "protein", "by", "cyclin-dependent", "kinases", "4", "and", "6", "prevents", "its", "interaction", "with", "the", "transcription", "factor", "E2F", ",", "which", "subsequently", "promotes", "the", "expression", "of", "S", "phase", "regulated", "genes", ",", "such", "as", "thymidine", "kinase", "." ]
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5150
[ "Although", "a", "role", "of", "p16", "in", "this", "regulation", "has", "been", "presumed", ",", "there", "is", "no", "proof", "so", "far", "that", "loss", "of", "this", "tumor", "suppressor", "gene", "really", "affects", "E2F", "-mediated", "regulations", "." ]
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