PubMed:16314839 JSONTXT

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":263,"end":271},"obj":"HP_0001909"}],"text":"Loss of interleukin-2-dependency in HTLV-I-infected T cells on gene silencing of thioredoxin-binding protein-2.\nThe transition from interleukin-2 (IL-2)-dependent to IL-2-independent growth is considered one of the key steps in the transformation of human T-cell leukemia virus type-I (HTLV-I)-infected T cells. The expression of thioredoxin-binding protein-2 (TBP-2) is lost during the transition of HTLV-I-infected T-cell lines. Here, we analysed the mechanism of loss of TBP-2 expression and the role of TBP-2 in IL-2-dependent growth in the in vitro model to investigate multistep transformation of HTLV-I. CpGs in the TBP-2 gene are methylated in IL-2-independent but not in IL-2-dependent cells. Sequential treatment with 5-aza-2'-deoxycytidine and a histone deacetylase inhibitor augmented histone acetylation and TBP-2 expression, suggesting that loss of TBP-2 expression is due to DNA methylation and histone deacetylation. In IL-2-dependent cells, a basal level of TBP-2 expression was maintained by IL-2 associated with cellular growth, whereas TBP-2 expression was upregulated on deprivation of IL-2 associated with growth suppression. Overexpression of TBP-2 in IL-2-independent cells suppressed the growth and partially restored responsiveness to IL-2. Knockdown of TBP-2 caused the IL-2-dependent cells to show partial growth without IL-2. These results suggested that epigenetic silencing of the TBP-2 gene results in a loss of responsiveness to IL-2, contributing to uncontrolled IL-2-independent growth in HTLV-I-infected T-cell lines."}

{"project":"bionlp-st-epi-2011-training","denotations":[{"id":"T1","span":{"begin":8,"end":21},"obj":"Protein"},{"id":"T2","span":{"begin":81,"end":110},"obj":"Protein"},{"id":"T3","span":{"begin":132,"end":145},"obj":"Protein"},{"id":"T4","span":{"begin":147,"end":151},"obj":"Protein"},{"id":"T5","span":{"begin":166,"end":170},"obj":"Protein"},{"id":"T6","span":{"begin":330,"end":359},"obj":"Protein"},{"id":"T7","span":{"begin":361,"end":366},"obj":"Protein"},{"id":"T8","span":{"begin":474,"end":479},"obj":"Protein"},{"id":"T9","span":{"begin":507,"end":512},"obj":"Protein"},{"id":"T10","span":{"begin":516,"end":520},"obj":"Protein"},{"id":"T11","span":{"begin":623,"end":628},"obj":"Protein"},{"id":"T12","span":{"begin":652,"end":656},"obj":"Protein"},{"id":"T13","span":{"begin":680,"end":684},"obj":"Protein"},{"id":"T14","span":{"begin":757,"end":764},"obj":"Protein"},{"id":"T15","span":{"begin":797,"end":804},"obj":"Protein"},{"id":"T16","span":{"begin":821,"end":826},"obj":"Protein"},{"id":"T17","span":{"begin":863,"end":868},"obj":"Protein"},{"id":"T18","span":{"begin":910,"end":917},"obj":"Protein"},{"id":"T19","span":{"begin":936,"end":940},"obj":"Protein"},{"id":"T20","span":{"begin":975,"end":980},"obj":"Protein"},{"id":"T21","span":{"begin":1010,"end":1014},"obj":"Protein"},{"id":"T22","span":{"begin":1056,"end":1061},"obj":"Protein"},{"id":"T23","span":{"begin":1107,"end":1111},"obj":"Protein"},{"id":"T24","span":{"begin":1166,"end":1171},"obj":"Protein"},{"id":"T25","span":{"begin":1175,"end":1179},"obj":"Protein"},{"id":"T26","span":{"begin":1261,"end":1265},"obj":"Protein"},{"id":"T27","span":{"begin":1280,"end":1285},"obj":"Protein"},{"id":"T28","span":{"begin":1297,"end":1301},"obj":"Protein"},{"id":"T29","span":{"begin":1349,"end":1353},"obj":"Protein"},{"id":"T30","span":{"begin":1412,"end":1417},"obj":"Protein"},{"id":"T31","span":{"begin":1462,"end":1466},"obj":"Protein"},{"id":"T32","span":{"begin":1497,"end":1501},"obj":"Protein"}],"text":"Loss of interleukin-2-dependency in HTLV-I-infected T cells on gene silencing of thioredoxin-binding protein-2.\nThe transition from interleukin-2 (IL-2)-dependent to IL-2-independent growth is considered one of the key steps in the transformation of human T-cell leukemia virus type-I (HTLV-I)-infected T cells. The expression of thioredoxin-binding protein-2 (TBP-2) is lost during the transition of HTLV-I-infected T-cell lines. Here, we analysed the mechanism of loss of TBP-2 expression and the role of TBP-2 in IL-2-dependent growth in the in vitro model to investigate multistep transformation of HTLV-I. CpGs in the TBP-2 gene are methylated in IL-2-independent but not in IL-2-dependent cells. Sequential treatment with 5-aza-2'-deoxycytidine and a histone deacetylase inhibitor augmented histone acetylation and TBP-2 expression, suggesting that loss of TBP-2 expression is due to DNA methylation and histone deacetylation. In IL-2-dependent cells, a basal level of TBP-2 expression was maintained by IL-2 associated with cellular growth, whereas TBP-2 expression was upregulated on deprivation of IL-2 associated with growth suppression. Overexpression of TBP-2 in IL-2-independent cells suppressed the growth and partially restored responsiveness to IL-2. Knockdown of TBP-2 caused the IL-2-dependent cells to show partial growth without IL-2. These results suggested that epigenetic silencing of the TBP-2 gene results in a loss of responsiveness to IL-2, contributing to uncontrolled IL-2-independent growth in HTLV-I-infected T-cell lines."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"16314839-1#20#33#gene3558","span":{"begin":132,"end":145},"obj":"gene3558"},{"id":"16314839-1#35#39#gene3558","span":{"begin":147,"end":151},"obj":"gene3558"},{"id":"16314839-1#54#58#gene3558","span":{"begin":166,"end":170},"obj":"gene3558"},{"id":"16314839-1#138#159#diseaseC0023493","span":{"begin":250,"end":271},"obj":"diseaseC0023493"}],"relations":[{"id":"20#33#gene3558138#159#diseaseC0023493","pred":"associated_with","subj":"16314839-1#20#33#gene3558","obj":"16314839-1#138#159#diseaseC0023493"},{"id":"35#39#gene3558138#159#diseaseC0023493","pred":"associated_with","subj":"16314839-1#35#39#gene3558","obj":"16314839-1#138#159#diseaseC0023493"},{"id":"54#58#gene3558138#159#diseaseC0023493","pred":"associated_with","subj":"16314839-1#54#58#gene3558","obj":"16314839-1#138#159#diseaseC0023493"}],"text":"Loss of interleukin-2-dependency in HTLV-I-infected T cells on gene silencing of thioredoxin-binding protein-2.\nThe transition from interleukin-2 (IL-2)-dependent to IL-2-independent growth is considered one of the key steps in the transformation of human T-cell leukemia virus type-I (HTLV-I)-infected T cells. The expression of thioredoxin-binding protein-2 (TBP-2) is lost during the transition of HTLV-I-infected T-cell lines. Here, we analysed the mechanism of loss of TBP-2 expression and the role of TBP-2 in IL-2-dependent growth in the in vitro model to investigate multistep transformation of HTLV-I. CpGs in the TBP-2 gene are methylated in IL-2-independent but not in IL-2-dependent cells. Sequential treatment with 5-aza-2'-deoxycytidine and a histone deacetylase inhibitor augmented histone acetylation and TBP-2 expression, suggesting that loss of TBP-2 expression is due to DNA methylation and histone deacetylation. In IL-2-dependent cells, a basal level of TBP-2 expression was maintained by IL-2 associated with cellular growth, whereas TBP-2 expression was upregulated on deprivation of IL-2 associated with growth suppression. Overexpression of TBP-2 in IL-2-independent cells suppressed the growth and partially restored responsiveness to IL-2. Knockdown of TBP-2 caused the IL-2-dependent cells to show partial growth without IL-2. These results suggested that epigenetic silencing of the TBP-2 gene results in a loss of responsiveness to IL-2, contributing to uncontrolled IL-2-independent growth in HTLV-I-infected T-cell lines."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":132,"end":145},"obj":"gene:3558"},{"id":"T1","span":{"begin":250,"end":271},"obj":"disease:C0023493"},{"id":"T2","span":{"begin":147,"end":151},"obj":"gene:3558"},{"id":"T3","span":{"begin":250,"end":271},"obj":"disease:C0023493"},{"id":"T4","span":{"begin":166,"end":170},"obj":"gene:3558"},{"id":"T5","span":{"begin":250,"end":271},"obj":"disease:C0023493"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"},{"id":"R3","pred":"associated_with","subj":"T4","obj":"T5"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Loss of interleukin-2-dependency in HTLV-I-infected T cells on gene silencing of thioredoxin-binding protein-2.\nThe transition from interleukin-2 (IL-2)-dependent to IL-2-independent growth is considered one of the key steps in the transformation of human T-cell leukemia virus type-I (HTLV-I)-infected T cells. The expression of thioredoxin-binding protein-2 (TBP-2) is lost during the transition of HTLV-I-infected T-cell lines. Here, we analysed the mechanism of loss of TBP-2 expression and the role of TBP-2 in IL-2-dependent growth in the in vitro model to investigate multistep transformation of HTLV-I. CpGs in the TBP-2 gene are methylated in IL-2-independent but not in IL-2-dependent cells. Sequential treatment with 5-aza-2'-deoxycytidine and a histone deacetylase inhibitor augmented histone acetylation and TBP-2 expression, suggesting that loss of TBP-2 expression is due to DNA methylation and histone deacetylation. In IL-2-dependent cells, a basal level of TBP-2 expression was maintained by IL-2 associated with cellular growth, whereas TBP-2 expression was upregulated on deprivation of IL-2 associated with growth suppression. Overexpression of TBP-2 in IL-2-independent cells suppressed the growth and partially restored responsiveness to IL-2. Knockdown of TBP-2 caused the IL-2-dependent cells to show partial growth without IL-2. These results suggested that epigenetic silencing of the TBP-2 gene results in a loss of responsiveness to IL-2, contributing to uncontrolled IL-2-independent growth in HTLV-I-infected T-cell lines."}