PubMed:21308745 JSON TXT

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PubTator4TogoVar

{"project":"PubTator4TogoVar","denotations":[{"id":"21308745_0","span":{"begin":229,"end":234},"obj":"ProteinMutation"}],"attributes":[{"id":"21308745_0_ProteinMutation","pred":"proteinmutation","subj":"21308745_0","obj":"rs17860424"}],"text":"Destabilization of CARP mRNAs by aloe-emodin contributes to caspase-8-mediated p53-independent apoptosis of human carcinoma cells.\nUsing short hairpin RNA against p53, transient ectopic expression of wild-type p53 or mutant p53 (R248W or R175H), and a p53- and p21-dependent luciferase reporter assay, we demonstrated that growth arrest and apoptosis of FaDu (human pharyngeal squamous cell carcinoma), Hep3B (hepatoma), and MG-63 (osteosarcoma) cells induced by aloe-emodin (AE) are p53-independent. Co-immunoprecipitation and small interfering RNA (siRNA) studies demonstrated that AE caused S-phase cell cycle arrest by inducing the formation of cyclin A-Cdk2-p21 complexes through extracellular signal-regulated kinase (ERK) activation. Ectopic expression of Bcl-X(L) and siRNA-mediated Bax attenuation significantly inhibited apoptosis induced by AE. Cyclosporin A or the caspase-8 inhibitor Z-IETD-FMK blocked AE-induced loss of mitochondrial membrane potential and prevented increases in reactive oxygen species and Ca(++). Z-IETD-FMK inhibited AE-induced apoptosis, Bax expression, Bid cleavage, translocation of tBid to mitochondria, ERK phosphorylation, caspase-9 activation, and the release of cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G from mitochondria. The stability of the mRNAs encoding caspase-8 and -10-associated RING proteins (CARPs) 1 and 2 was affected by AE, whereas CARP1 or 2 overexpression inhibited caspase-8 activation and apoptosis induced by AE. Collectively, our data indicate AE induces caspase-8-mediated activation of mitochondrial death pathways by decreasing the stability of CARP mRNAs in a p53-independent manner."}

DisGeNET

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":224,"end":227},"obj":"gene:7157"},{"id":"T1","span":{"begin":366,"end":400},"obj":"disease:C1319317"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Destabilization of CARP mRNAs by aloe-emodin contributes to caspase-8-mediated p53-independent apoptosis of human carcinoma cells.\nUsing short hairpin RNA against p53, transient ectopic expression of wild-type p53 or mutant p53 (R248W or R175H), and a p53- and p21-dependent luciferase reporter assay, we demonstrated that growth arrest and apoptosis of FaDu (human pharyngeal squamous cell carcinoma), Hep3B (hepatoma), and MG-63 (osteosarcoma) cells induced by aloe-emodin (AE) are p53-independent. Co-immunoprecipitation and small interfering RNA (siRNA) studies demonstrated that AE caused S-phase cell cycle arrest by inducing the formation of cyclin A-Cdk2-p21 complexes through extracellular signal-regulated kinase (ERK) activation. Ectopic expression of Bcl-X(L) and siRNA-mediated Bax attenuation significantly inhibited apoptosis induced by AE. Cyclosporin A or the caspase-8 inhibitor Z-IETD-FMK blocked AE-induced loss of mitochondrial membrane potential and prevented increases in reactive oxygen species and Ca(++). Z-IETD-FMK inhibited AE-induced apoptosis, Bax expression, Bid cleavage, translocation of tBid to mitochondria, ERK phosphorylation, caspase-9 activation, and the release of cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G from mitochondria. The stability of the mRNAs encoding caspase-8 and -10-associated RING proteins (CARPs) 1 and 2 was affected by AE, whereas CARP1 or 2 overexpression inhibited caspase-8 activation and apoptosis induced by AE. Collectively, our data indicate AE induces caspase-8-mediated activation of mitochondrial death pathways by decreasing the stability of CARP mRNAs in a p53-independent manner."}

PubmedHPO

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":377,"end":400},"obj":"HP_0002860"},{"id":"T2","span":{"begin":432,"end":444},"obj":"HP_0002669"},{"id":"T3","span":{"begin":935,"end":948},"obj":"HP_0001427"},{"id":"T4","span":{"begin":1575,"end":1588},"obj":"HP_0001427"}],"text":"Destabilization of CARP mRNAs by aloe-emodin contributes to caspase-8-mediated p53-independent apoptosis of human carcinoma cells.\nUsing short hairpin RNA against p53, transient ectopic expression of wild-type p53 or mutant p53 (R248W or R175H), and a p53- and p21-dependent luciferase reporter assay, we demonstrated that growth arrest and apoptosis of FaDu (human pharyngeal squamous cell carcinoma), Hep3B (hepatoma), and MG-63 (osteosarcoma) cells induced by aloe-emodin (AE) are p53-independent. Co-immunoprecipitation and small interfering RNA (siRNA) studies demonstrated that AE caused S-phase cell cycle arrest by inducing the formation of cyclin A-Cdk2-p21 complexes through extracellular signal-regulated kinase (ERK) activation. Ectopic expression of Bcl-X(L) and siRNA-mediated Bax attenuation significantly inhibited apoptosis induced by AE. Cyclosporin A or the caspase-8 inhibitor Z-IETD-FMK blocked AE-induced loss of mitochondrial membrane potential and prevented increases in reactive oxygen species and Ca(++). Z-IETD-FMK inhibited AE-induced apoptosis, Bax expression, Bid cleavage, translocation of tBid to mitochondria, ERK phosphorylation, caspase-9 activation, and the release of cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G from mitochondria. The stability of the mRNAs encoding caspase-8 and -10-associated RING proteins (CARPs) 1 and 2 was affected by AE, whereas CARP1 or 2 overexpression inhibited caspase-8 activation and apoptosis induced by AE. Collectively, our data indicate AE induces caspase-8-mediated activation of mitochondrial death pathways by decreasing the stability of CARP mRNAs in a p53-independent manner."}

Allie

{"project":"Allie","denotations":[{"id":"SS1_21308745_1_0","span":{"begin":463,"end":474},"obj":"expanded"},{"id":"SS2_21308745_1_0","span":{"begin":476,"end":478},"obj":"abbr"},{"id":"SS1_21308745_2_0","span":{"begin":528,"end":549},"obj":"expanded"},{"id":"SS2_21308745_2_0","span":{"begin":551,"end":556},"obj":"abbr"},{"id":"SS1_21308745_2_1","span":{"begin":685,"end":722},"obj":"expanded"},{"id":"SS2_21308745_2_1","span":{"begin":724,"end":727},"obj":"abbr"},{"id":"SS1_21308745_5_0","span":{"begin":1219,"end":1244},"obj":"expanded"},{"id":"SS2_21308745_5_0","span":{"begin":1246,"end":1249},"obj":"abbr"},{"id":"SS1_21308745_6_0","span":{"begin":1326,"end":1368},"obj":"expanded"},{"id":"SS2_21308745_6_0","span":{"begin":1370,"end":1375},"obj":"abbr"}],"relations":[{"id":"AE1_21308745_1_0","pred":"abbreviatedTo","subj":"SS1_21308745_1_0","obj":"SS2_21308745_1_0"},{"id":"AE1_21308745_2_0","pred":"abbreviatedTo","subj":"SS1_21308745_2_0","obj":"SS2_21308745_2_0"},{"id":"AE1_21308745_2_1","pred":"abbreviatedTo","subj":"SS1_21308745_2_1","obj":"SS2_21308745_2_1"},{"id":"AE1_21308745_5_0","pred":"abbreviatedTo","subj":"SS1_21308745_5_0","obj":"SS2_21308745_5_0"},{"id":"AE1_21308745_6_0","pred":"abbreviatedTo","subj":"SS1_21308745_6_0","obj":"SS2_21308745_6_0"}],"text":"Destabilization of CARP mRNAs by aloe-emodin contributes to caspase-8-mediated p53-independent apoptosis of human carcinoma cells.\nUsing short hairpin RNA against p53, transient ectopic expression of wild-type p53 or mutant p53 (R248W or R175H), and a p53- and p21-dependent luciferase reporter assay, we demonstrated that growth arrest and apoptosis of FaDu (human pharyngeal squamous cell carcinoma), Hep3B (hepatoma), and MG-63 (osteosarcoma) cells induced by aloe-emodin (AE) are p53-independent. Co-immunoprecipitation and small interfering RNA (siRNA) studies demonstrated that AE caused S-phase cell cycle arrest by inducing the formation of cyclin A-Cdk2-p21 complexes through extracellular signal-regulated kinase (ERK) activation. Ectopic expression of Bcl-X(L) and siRNA-mediated Bax attenuation significantly inhibited apoptosis induced by AE. Cyclosporin A or the caspase-8 inhibitor Z-IETD-FMK blocked AE-induced loss of mitochondrial membrane potential and prevented increases in reactive oxygen species and Ca(++). Z-IETD-FMK inhibited AE-induced apoptosis, Bax expression, Bid cleavage, translocation of tBid to mitochondria, ERK phosphorylation, caspase-9 activation, and the release of cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G from mitochondria. The stability of the mRNAs encoding caspase-8 and -10-associated RING proteins (CARPs) 1 and 2 was affected by AE, whereas CARP1 or 2 overexpression inhibited caspase-8 activation and apoptosis induced by AE. Collectively, our data indicate AE induces caspase-8-mediated activation of mitochondrial death pathways by decreasing the stability of CARP mRNAs in a p53-independent manner."}

DisGeNET5_variant_disease

{"project":"DisGeNET5_variant_disease","denotations":[{"id":"21308745-1#107#112#geners2308950","span":{"begin":238,"end":243},"obj":"geners2308950"},{"id":"21308745-1#107#112#geners28934578","span":{"begin":238,"end":243},"obj":"geners28934578"},{"id":"21308745-1#107#112#geners573154688","span":{"begin":238,"end":243},"obj":"geners573154688"},{"id":"21308745-1#235#269#diseaseC1319317","span":{"begin":366,"end":400},"obj":"diseaseC1319317"}],"relations":[{"id":"107#112#geners2308950235#269#diseaseC1319317","pred":"associated_with","subj":"21308745-1#107#112#geners2308950","obj":"21308745-1#235#269#diseaseC1319317"},{"id":"107#112#geners28934578235#269#diseaseC1319317","pred":"associated_with","subj":"21308745-1#107#112#geners28934578","obj":"21308745-1#235#269#diseaseC1319317"},{"id":"107#112#geners573154688235#269#diseaseC1319317","pred":"associated_with","subj":"21308745-1#107#112#geners573154688","obj":"21308745-1#235#269#diseaseC1319317"}],"text":"Destabilization of CARP mRNAs by aloe-emodin contributes to caspase-8-mediated p53-independent apoptosis of human carcinoma cells.\nUsing short hairpin RNA against p53, transient ectopic expression of wild-type p53 or mutant p53 (R248W or R175H), and a p53- and p21-dependent luciferase reporter assay, we demonstrated that growth arrest and apoptosis of FaDu (human pharyngeal squamous cell carcinoma), Hep3B (hepatoma), and MG-63 (osteosarcoma) cells induced by aloe-emodin (AE) are p53-independent. Co-immunoprecipitation and small interfering RNA (siRNA) studies demonstrated that AE caused S-phase cell cycle arrest by inducing the formation of cyclin A-Cdk2-p21 complexes through extracellular signal-regulated kinase (ERK) activation. Ectopic expression of Bcl-X(L) and siRNA-mediated Bax attenuation significantly inhibited apoptosis induced by AE. Cyclosporin A or the caspase-8 inhibitor Z-IETD-FMK blocked AE-induced loss of mitochondrial membrane potential and prevented increases in reactive oxygen species and Ca(++). Z-IETD-FMK inhibited AE-induced apoptosis, Bax expression, Bid cleavage, translocation of tBid to mitochondria, ERK phosphorylation, caspase-9 activation, and the release of cytochrome c, apoptosis-inducing factor (AIF), and endonuclease G from mitochondria. The stability of the mRNAs encoding caspase-8 and -10-associated RING proteins (CARPs) 1 and 2 was affected by AE, whereas CARP1 or 2 overexpression inhibited caspase-8 activation and apoptosis induced by AE. Collectively, our data indicate AE induces caspase-8-mediated activation of mitochondrial death pathways by decreasing the stability of CARP mRNAs in a p53-independent manner."}

DisGeNET5_gene_disease