PubMed:24998848 JSONTXT

{"project":"Inflammaging","denotations":[{"id":"T1","span":{"begin":0,"end":128},"obj":"Sentence"},{"id":"T2","span":{"begin":129,"end":198},"obj":"Sentence"},{"id":"T3","span":{"begin":199,"end":296},"obj":"Sentence"},{"id":"T4","span":{"begin":297,"end":505},"obj":"Sentence"},{"id":"T5","span":{"begin":506,"end":624},"obj":"Sentence"},{"id":"T6","span":{"begin":625,"end":893},"obj":"Sentence"},{"id":"T7","span":{"begin":894,"end":1077},"obj":"Sentence"},{"id":"T8","span":{"begin":1078,"end":1301},"obj":"Sentence"},{"id":"T1","span":{"begin":0,"end":128},"obj":"Sentence"},{"id":"T2","span":{"begin":129,"end":198},"obj":"Sentence"},{"id":"T3","span":{"begin":199,"end":296},"obj":"Sentence"},{"id":"T4","span":{"begin":297,"end":505},"obj":"Sentence"},{"id":"T5","span":{"begin":506,"end":624},"obj":"Sentence"},{"id":"T6","span":{"begin":625,"end":893},"obj":"Sentence"},{"id":"T7","span":{"begin":894,"end":1077},"obj":"Sentence"},{"id":"T8","span":{"begin":1078,"end":1301},"obj":"Sentence"}],"text":"Mutant p53 gains new function in promoting inflammatory signals by repression of the secreted interleukin-1 receptor antagonist.\nThe TP53 tumor-suppressor gene is frequently mutated in human cancer. Missense mutations can add novel functions (gain-of-function, GOF) that promote tumor malignancy. Here we report that mutant (mut) p53 promotes tumor malignancy by suppressing the expression of a natural occurring anti-inflammatory cytokine, the secreted interleukin-1 receptor antagonist (sIL-1Ra, IL1RN). We show that mutp53 but not wild-type (wt) p53 suppresses the sIL-1Ra production in conditioned media of cancer cells. Moreover, mutp53, but not wtp53, binds physically the sIL-1Ra promoter and the protein-protein interaction with the transcriptional co-repressor MAFF (v-MAF musculoaponeurotic fibrosarcoma oncogene family, protein F) is required for mutp53-induced sIL-1Ra suppression. Remarkably, when exposed to IL-1 beta (IL-1β) inflammatory stimuli, mutp53 sustains a ready-to-be-activated in vitro and in vivo cancer cells' response through the sIL-1Ra repression. Taken together, these results identify sIL-1Ra as a novel mutp53 target gene, whose suppression might be required to generate a chronic pro-inflammatory tumor microenvironment through which mutp53 promotes tumor malignancy."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":138,"end":143},"obj":"HP_0002664"},{"id":"T2","span":{"begin":191,"end":197},"obj":"HP_0002664"},{"id":"T3","span":{"begin":279,"end":284},"obj":"HP_0002664"},{"id":"T4","span":{"begin":343,"end":348},"obj":"HP_0002664"},{"id":"T5","span":{"begin":611,"end":617},"obj":"HP_0002664"},{"id":"T6","span":{"begin":801,"end":813},"obj":"HP_0100244"},{"id":"T7","span":{"begin":1023,"end":1029},"obj":"HP_0002664"},{"id":"T8","span":{"begin":1231,"end":1236},"obj":"HP_0002664"},{"id":"T9","span":{"begin":1284,"end":1289},"obj":"HP_0002664"}],"text":"Mutant p53 gains new function in promoting inflammatory signals by repression of the secreted interleukin-1 receptor antagonist.\nThe TP53 tumor-suppressor gene is frequently mutated in human cancer. Missense mutations can add novel functions (gain-of-function, GOF) that promote tumor malignancy. Here we report that mutant (mut) p53 promotes tumor malignancy by suppressing the expression of a natural occurring anti-inflammatory cytokine, the secreted interleukin-1 receptor antagonist (sIL-1Ra, IL1RN). We show that mutp53 but not wild-type (wt) p53 suppresses the sIL-1Ra production in conditioned media of cancer cells. Moreover, mutp53, but not wtp53, binds physically the sIL-1Ra promoter and the protein-protein interaction with the transcriptional co-repressor MAFF (v-MAF musculoaponeurotic fibrosarcoma oncogene family, protein F) is required for mutp53-induced sIL-1Ra suppression. Remarkably, when exposed to IL-1 beta (IL-1β) inflammatory stimuli, mutp53 sustains a ready-to-be-activated in vitro and in vivo cancer cells' response through the sIL-1Ra repression. Taken together, these results identify sIL-1Ra as a novel mutp53 target gene, whose suppression might be required to generate a chronic pro-inflammatory tumor microenvironment through which mutp53 promotes tumor malignancy."}

{"project":"kaiyin_test","denotations":[{"id":"T2","span":{"begin":133,"end":159},"obj":"Gene"},{"id":"T1","span":{"begin":199,"end":217},"obj":"Var"},{"id":"T3","span":{"begin":271,"end":278},"obj":"PosReg"},{"id":"T4","span":{"begin":279,"end":295},"obj":"CPA"},{"id":"T5","span":{"begin":317,"end":323},"obj":"Var"},{"id":"T6","span":{"begin":330,"end":333},"obj":"Gene"},{"id":"T7","span":{"begin":334,"end":342},"obj":"PosReg"},{"id":"T8","span":{"begin":343,"end":359},"obj":"CPA"},{"id":"T9","span":{"begin":363,"end":374},"obj":"NegReg"},{"id":"T10","span":{"begin":379,"end":439},"obj":"MPA"},{"id":"T11","span":{"begin":519,"end":525},"obj":"Var"},{"id":"T12","span":{"begin":553,"end":563},"obj":"NegReg"},{"id":"T13","span":{"begin":568,"end":586},"obj":"MPA"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T2","obj":"T1"},{"id":"R10","pred":"ThemeOf","subj":"T13","obj":"T12"},{"id":"R2","pred":"CauseOf","subj":"T1","obj":"T3"},{"id":"R3","pred":"ThemeOf","subj":"T4","obj":"T3"},{"id":"R4","pred":"ThemeOf","subj":"T6","obj":"T5"},{"id":"R5","pred":"CauseOf","subj":"T5","obj":"T9"},{"id":"R6","pred":"ThemeOf","subj":"T10","obj":"T9"},{"id":"R7","pred":"CauseOf","subj":"T9","obj":"T7"},{"id":"R8","pred":"ThemeOf","subj":"T8","obj":"T7"},{"id":"R9","pred":"CauseOf","subj":"T11","obj":"T12"}],"text":"Mutant p53 gains new function in promoting inflammatory signals by repression of the secreted interleukin-1 receptor antagonist.\nThe TP53 tumor-suppressor gene is frequently mutated in human cancer. Missense mutations can add novel functions (gain-of-function, GOF) that promote tumor malignancy. Here we report that mutant (mut) p53 promotes tumor malignancy by suppressing the expression of a natural occurring anti-inflammatory cytokine, the secreted interleukin-1 receptor antagonist (sIL-1Ra, IL1RN). We show that mutp53 but not wild-type (wt) p53 suppresses the sIL-1Ra production in conditioned media of cancer cells. Moreover, mutp53, but not wtp53, binds physically the sIL-1Ra promoter and the protein-protein interaction with the transcriptional co-repressor MAFF (v-MAF musculoaponeurotic fibrosarcoma oncogene family, protein F) is required for mutp53-induced sIL-1Ra suppression. Remarkably, when exposed to IL-1 beta (IL-1β) inflammatory stimuli, mutp53 sustains a ready-to-be-activated in vitro and in vivo cancer cells' response through the sIL-1Ra repression. Taken together, these results identify sIL-1Ra as a novel mutp53 target gene, whose suppression might be required to generate a chronic pro-inflammatory tumor microenvironment through which mutp53 promotes tumor malignancy."}

{"project":"name_no","denotations":[{"id":"T2","span":{"begin":133,"end":159},"obj":"Gene"},{"id":"T1","span":{"begin":199,"end":217},"obj":"Var"},{"id":"T3","span":{"begin":271,"end":278},"obj":"PosReg"},{"id":"T4","span":{"begin":279,"end":295},"obj":"CPA"},{"id":"T5","span":{"begin":317,"end":323},"obj":"Var"},{"id":"T6","span":{"begin":330,"end":333},"obj":"Gene"},{"id":"T7","span":{"begin":334,"end":342},"obj":"PosReg"},{"id":"T8","span":{"begin":343,"end":359},"obj":"CPA"},{"id":"T9","span":{"begin":363,"end":374},"obj":"NegReg"},{"id":"T10","span":{"begin":379,"end":439},"obj":"MPA"},{"id":"T11","span":{"begin":519,"end":525},"obj":"Var"},{"id":"T12","span":{"begin":553,"end":563},"obj":"NegReg"},{"id":"T13","span":{"begin":568,"end":586},"obj":"MPA"}],"relations":[{"id":"R1","pred":"ThemeOf","subj":"T2","obj":"T1"},{"id":"R10","pred":"ThemeOf","subj":"T13","obj":"T12"},{"id":"R2","pred":"CauseOf","subj":"T1","obj":"T3"},{"id":"R3","pred":"ThemeOf","subj":"T4","obj":"T3"},{"id":"R4","pred":"ThemeOf","subj":"T6","obj":"T5"},{"id":"R5","pred":"CauseOf","subj":"T5","obj":"T9"},{"id":"R6","pred":"ThemeOf","subj":"T10","obj":"T9"},{"id":"R7","pred":"CauseOf","subj":"T9","obj":"T7"},{"id":"R8","pred":"ThemeOf","subj":"T8","obj":"T7"},{"id":"R9","pred":"CauseOf","subj":"T11","obj":"T12"}],"text":"Mutant p53 gains new function in promoting inflammatory signals by repression of the secreted interleukin-1 receptor antagonist.\nThe TP53 tumor-suppressor gene is frequently mutated in human cancer. Missense mutations can add novel functions (gain-of-function, GOF) that promote tumor malignancy. Here we report that mutant (mut) p53 promotes tumor malignancy by suppressing the expression of a natural occurring anti-inflammatory cytokine, the secreted interleukin-1 receptor antagonist (sIL-1Ra, IL1RN). We show that mutp53 but not wild-type (wt) p53 suppresses the sIL-1Ra production in conditioned media of cancer cells. Moreover, mutp53, but not wtp53, binds physically the sIL-1Ra promoter and the protein-protein interaction with the transcriptional co-repressor MAFF (v-MAF musculoaponeurotic fibrosarcoma oncogene family, protein F) is required for mutp53-induced sIL-1Ra suppression. Remarkably, when exposed to IL-1 beta (IL-1β) inflammatory stimuli, mutp53 sustains a ready-to-be-activated in vitro and in vivo cancer cells' response through the sIL-1Ra repression. Taken together, these results identify sIL-1Ra as a novel mutp53 target gene, whose suppression might be required to generate a chronic pro-inflammatory tumor microenvironment through which mutp53 promotes tumor malignancy."}