PubMed:10075927 JSONTXT

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":14,"end":16},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":480,"end":482},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":771,"end":773},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":843,"end":845},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T5","span":{"begin":944,"end":946},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T6","span":{"begin":1197,"end":1199},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T7","span":{"begin":1257,"end":1259},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0008380"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0008380"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0008380"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0008380"},{"id":"A5","pred":"mondo_id","subj":"T5","obj":"0008380"},{"id":"A6","pred":"mondo_id","subj":"T6","obj":"0008380"},{"id":"A7","pred":"mondo_id","subj":"T7","obj":"0008380"}],"text":"Regulation of Rb and E2F by signal transduction cascades: divergent effects of JNK1 and p38 kinases.\nThe E2F transcription factor plays a major role in cell cycle regulation, differentiation and apoptosis, but it is not clear how it is regulated by non-mitogenic signaling cascades. Here we report that two kinases involved in signal transduction have opposite effects on E2F function: the stress-induced kinase JNK1 inhibits E2F1 activity whereas the related p38 kinase reverses Rb-mediated repression of E2F1. JNK1 phosphorylates E2F1 in vitro, and co-transfection of JNK1 reduces the DNA binding activity of E2F1; treatment of cells with TNFalpha had a similar effect. Fas stimulation of Jurkat cells is known to induce p38 kinase and we find a pronounced increase in Rb phosphorylation within 30 min of Fas stimulation. Phosphorylation of Rb correlated with a dissociation of E2F and increased transcriptional activity. The inactivation of Rb by Fas was blocked by SB203580, a p38-specific inhibitor, as well as a dominant-negative p38 construct; cyclin-dependent kinase (cdk) inhibitors as well as dominant-negative cdks had no effect. These results suggest that Fas-mediated inactivation of Rb is mediated via the p38 kinase, independent of cdks. The Rb/E2F-mediated cell cycle regulatory pathway appears to be a normal target for non-mitogenic signaling cascades and could be involved in mediating the cellular effects of such signals."}

{"project":"2015-BEL-Sample","denotations":[{"id":"T1","span":{"begin":672,"end":822},"obj":"cat(p(HGNC:FAS)) increases p(HGNC:RB1,pmod(P))"}],"text":"Regulation of Rb and E2F by signal transduction cascades: divergent effects of JNK1 and p38 kinases.\nThe E2F transcription factor plays a major role in cell cycle regulation, differentiation and apoptosis, but it is not clear how it is regulated by non-mitogenic signaling cascades. Here we report that two kinases involved in signal transduction have opposite effects on E2F function: the stress-induced kinase JNK1 inhibits E2F1 activity whereas the related p38 kinase reverses Rb-mediated repression of E2F1. JNK1 phosphorylates E2F1 in vitro, and co-transfection of JNK1 reduces the DNA binding activity of E2F1; treatment of cells with TNFalpha had a similar effect. Fas stimulation of Jurkat cells is known to induce p38 kinase and we find a pronounced increase in Rb phosphorylation within 30 min of Fas stimulation. Phosphorylation of Rb correlated with a dissociation of E2F and increased transcriptional activity. The inactivation of Rb by Fas was blocked by SB203580, a p38-specific inhibitor, as well as a dominant-negative p38 construct; cyclin-dependent kinase (cdk) inhibitors as well as dominant-negative cdks had no effect. These results suggest that Fas-mediated inactivation of Rb is mediated via the p38 kinase, independent of cdks. The Rb/E2F-mediated cell cycle regulatory pathway appears to be a normal target for non-mitogenic signaling cascades and could be involved in mediating the cellular effects of such signals."}

{"project":"2015-BEL-Sample-2","denotations":[{"id":"BEL:20000048","span":{"begin":672,"end":822},"obj":"cat(p(HGNC:FAS)) increases p(HGNC:RB1,pmod(P))"},{"id":"BEL:20006082","span":{"begin":672,"end":821},"obj":"cat(p(HGNC:FAS)) increases p(HGNC:RB1,pmod(P))"},{"id":"BEL:20029764","span":{"begin":672,"end":821},"obj":"cat(p(HGNC:FAS)) increases kin(p(HGNC:MAPK14))"},{"id":"BEL:20029794","span":{"begin":672,"end":821},"obj":"cat(p(HGNC:FAS)) decreases tscript(p(HGNC:RB1))"},{"id":"BEL:20036960","span":{"begin":1141,"end":1250},"obj":"kin(p(HGNC:MAPK14)) increases p(HGNC:RB1,pmod(P))"},{"id":"BEL:20036978","span":{"begin":1141,"end":1250},"obj":"kin(p(HGNC:MAPK14)) decreases tscript(p(HGNC:RB1))"},{"id":"BEL:20037072","span":{"begin":512,"end":615},"obj":"kin(p(HGNC:MAPK8)) increases p(HGNC:E2F1,pmod(P))"},{"id":"BEL:20037088","span":{"begin":512,"end":615},"obj":"kin(p(HGNC:MAPK8)) decreases tscript(p(HGNC:E2F1))"},{"id":"BEL:20011414","span":{"begin":672,"end":821},"obj":"p(HGNC:RB1,pmod(P)) directlyDecreases tscript(p(HGNC:RB1))"}],"text":"Regulation of Rb and E2F by signal transduction cascades: divergent effects of JNK1 and p38 kinases.\nThe E2F transcription factor plays a major role in cell cycle regulation, differentiation and apoptosis, but it is not clear how it is regulated by non-mitogenic signaling cascades. Here we report that two kinases involved in signal transduction have opposite effects on E2F function: the stress-induced kinase JNK1 inhibits E2F1 activity whereas the related p38 kinase reverses Rb-mediated repression of E2F1. JNK1 phosphorylates E2F1 in vitro, and co-transfection of JNK1 reduces the DNA binding activity of E2F1; treatment of cells with TNFalpha had a similar effect. Fas stimulation of Jurkat cells is known to induce p38 kinase and we find a pronounced increase in Rb phosphorylation within 30 min of Fas stimulation. Phosphorylation of Rb correlated with a dissociation of E2F and increased transcriptional activity. The inactivation of Rb by Fas was blocked by SB203580, a p38-specific inhibitor, as well as a dominant-negative p38 construct; cyclin-dependent kinase (cdk) inhibitors as well as dominant-negative cdks had no effect. These results suggest that Fas-mediated inactivation of Rb is mediated via the p38 kinase, independent of cdks. The Rb/E2F-mediated cell cycle regulatory pathway appears to be a normal target for non-mitogenic signaling cascades and could be involved in mediating the cellular effects of such signals."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":412,"end":416},"obj":"gene:5599"},{"id":"T1","span":{"begin":390,"end":396},"obj":"disease:C3825627"},{"id":"T2","span":{"begin":506,"end":510},"obj":"gene:1869"},{"id":"T3","span":{"begin":390,"end":396},"obj":"disease:C3825627"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"},{"id":"R2","pred":"associated_with","subj":"T2","obj":"T3"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Regulation of Rb and E2F by signal transduction cascades: divergent effects of JNK1 and p38 kinases.\nThe E2F transcription factor plays a major role in cell cycle regulation, differentiation and apoptosis, but it is not clear how it is regulated by non-mitogenic signaling cascades. Here we report that two kinases involved in signal transduction have opposite effects on E2F function: the stress-induced kinase JNK1 inhibits E2F1 activity whereas the related p38 kinase reverses Rb-mediated repression of E2F1. JNK1 phosphorylates E2F1 in vitro, and co-transfection of JNK1 reduces the DNA binding activity of E2F1; treatment of cells with TNFalpha had a similar effect. Fas stimulation of Jurkat cells is known to induce p38 kinase and we find a pronounced increase in Rb phosphorylation within 30 min of Fas stimulation. Phosphorylation of Rb correlated with a dissociation of E2F and increased transcriptional activity. The inactivation of Rb by Fas was blocked by SB203580, a p38-specific inhibitor, as well as a dominant-negative p38 construct; cyclin-dependent kinase (cdk) inhibitors as well as dominant-negative cdks had no effect. These results suggest that Fas-mediated inactivation of Rb is mediated via the p38 kinase, independent of cdks. The Rb/E2F-mediated cell cycle regulatory pathway appears to be a normal target for non-mitogenic signaling cascades and could be involved in mediating the cellular effects of such signals."}