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Therefore, the ability of Akt and mTORC1 inhibitors to block the increase in TNFα mRNA lead us to examine their role in the activation of JNK during necroptosis. Knockdown of Akt isoforms Akt1 and Akt2 or inhibition of Akt prominently suppressed the necroptosis dependent increase in JNK and c-Jun phosphorylation (Fig. 6E, S6D,E) suggesting that Akt may provide a link between RIP1 and JNK activation. Importantly, inhibition of Akt only inhibited the delayed, but not the early, increase in bFGF/zVAD.fmk induced JNK and c-Jun phosphorylation (Fig. S6F). Knockdown of mTOR, rapamycin and the p70S6K inhibitor PF-4708671 also attenuated the necroptosis-associated increase in JNK and c-Jun phosphorylation (Fig. 6F, S6E,G, Fig. S5D). Overall, these data suggested that the Akt-mTORC1-S6K axis, acting downstream from RIP1 kinase, is required for the increase in JNK activity during necroptosis in L929 cells."}

{"project":"bionlp-st-ge-2016-test-proteins","denotations":[{"id":"T11897","span":{"begin":920,"end":924},"obj":"Protein"},{"id":"T11896","span":{"begin":887,"end":890},"obj":"Protein"},{"id":"T11895","span":{"begin":787,"end":792},"obj":"Protein"},{"id":"T11894","span":{"begin":696,"end":702},"obj":"Protein"},{"id":"T11893","span":{"begin":625,"end":630},"obj":"Protein"},{"id":"T11892","span":{"begin":595,"end":599},"obj":"Protein"},{"id":"T11891","span":{"begin":480,"end":484},"obj":"Protein"},{"id":"T11890","span":{"begin":394,"end":399},"obj":"Protein"},{"id":"T11889","span":{"begin":299,"end":303},"obj":"Protein"},{"id":"T11888","span":{"begin":290,"end":294},"obj":"Protein"},{"id":"T11887","span":{"begin":179,"end":183},"obj":"Protein"},{"id":"T11886","span":{"begin":39,"end":43},"obj":"Protein"}],"namespaces":[{"prefix":"_base","uri":"http://bionlp.dbcls.jp/ontology/ge.owl#"}],"text":"JNK is a well-established regulator of TNFα synthesis in a variety of systems [13], [14], [15], [34]. Therefore, the ability of Akt and mTORC1 inhibitors to block the increase in TNFα mRNA lead us to examine their role in the activation of JNK during necroptosis. Knockdown of Akt isoforms Akt1 and Akt2 or inhibition of Akt prominently suppressed the necroptosis dependent increase in JNK and c-Jun phosphorylation (Fig. 6E, S6D,E) suggesting that Akt may provide a link between RIP1 and JNK activation. Importantly, inhibition of Akt only inhibited the delayed, but not the early, increase in bFGF/zVAD.fmk induced JNK and c-Jun phosphorylation (Fig. S6F). Knockdown of mTOR, rapamycin and the p70S6K inhibitor PF-4708671 also attenuated the necroptosis-associated increase in JNK and c-Jun phosphorylation (Fig. 6F, S6E,G, Fig. S5D). Overall, these data suggested that the Akt-mTORC1-S6K axis, acting downstream from RIP1 kinase, is required for the increase in JNK activity during necroptosis in L929 cells."}

{"project":"bionlp-st-ge-2016-uniprot","denotations":[{"id":"T12278","span":{"begin":672,"end":676},"obj":"http://www.uniprot.org/uniprot/P42345"},{"id":"T12277","span":{"begin":595,"end":599},"obj":"http://www.uniprot.org/uniprot/Q788Q8"},{"id":"T12276","span":{"begin":920,"end":924},"obj":"http://www.uniprot.org/uniprot/Q13546"},{"id":"T12275","span":{"begin":480,"end":484},"obj":"http://www.uniprot.org/uniprot/Q13546"},{"id":"T12274","span":{"begin":787,"end":792},"obj":"http://www.uniprot.org/uniprot/P05412"},{"id":"T12273","span":{"begin":625,"end":630},"obj":"http://www.uniprot.org/uniprot/P05412"},{"id":"T12272","span":{"begin":394,"end":399},"obj":"http://www.uniprot.org/uniprot/P05412"},{"id":"T12271","span":{"begin":179,"end":183},"obj":"http://www.uniprot.org/uniprot/P01375"},{"id":"T12270","span":{"begin":39,"end":43},"obj":"http://www.uniprot.org/uniprot/P01375"},{"id":"T12269","span":{"begin":876,"end":879},"obj":"http://www.uniprot.org/uniprot/Q9Y243"},{"id":"T12268","span":{"begin":532,"end":535},"obj":"http://www.uniprot.org/uniprot/Q9Y243"},{"id":"T12267","span":{"begin":449,"end":452},"obj":"http://www.uniprot.org/uniprot/Q9Y243"},{"id":"T12266","span":{"begin":321,"end":324},"obj":"http://www.uniprot.org/uniprot/Q9Y243"},{"id":"T12265","span":{"begin":277,"end":280},"obj":"http://www.uniprot.org/uniprot/Q9Y243"},{"id":"T12264","span":{"begin":128,"end":131},"obj":"http://www.uniprot.org/uniprot/Q9Y243"},{"id":"T12262","span":{"begin":876,"end":879},"obj":"http://www.uniprot.org/uniprot/P31751"},{"id":"T12261","span":{"begin":532,"end":535},"obj":"http://www.uniprot.org/uniprot/P31751"},{"id":"T12260","span":{"begin":449,"end":452},"obj":"http://www.uniprot.org/uniprot/P31751"},{"id":"T12259","span":{"begin":321,"end":324},"obj":"http://www.uniprot.org/uniprot/P31751"},{"id":"T12258","span":{"begin":277,"end":280},"obj":"http://www.uniprot.org/uniprot/P31751"},{"id":"T12257","span":{"begin":128,"end":131},"obj":"http://www.uniprot.org/uniprot/P31751"},{"id":"T12255","span":{"begin":876,"end":879},"obj":"http://www.uniprot.org/uniprot/P31749"},{"id":"T12254","span":{"begin":532,"end":535},"obj":"http://www.uniprot.org/uniprot/P31749"},{"id":"T12253","span":{"begin":449,"end":452},"obj":"http://www.uniprot.org/uniprot/P31749"},{"id":"T12252","span":{"begin":321,"end":324},"obj":"http://www.uniprot.org/uniprot/P31749"},{"id":"T12251","span":{"begin":277,"end":280},"obj":"http://www.uniprot.org/uniprot/P31749"},{"id":"T12250","span":{"begin":128,"end":131},"obj":"http://www.uniprot.org/uniprot/P31749"}],"namespaces":[{"prefix":"_base","uri":"http://www.uniprot.org/uniprot/"}],"text":"JNK is a well-established regulator of TNFα synthesis in a variety of systems [13], [14], [15], [34]. Therefore, the ability of Akt and mTORC1 inhibitors to block the increase in TNFα mRNA lead us to examine their role in the activation of JNK during necroptosis. Knockdown of Akt isoforms Akt1 and Akt2 or inhibition of Akt prominently suppressed the necroptosis dependent increase in JNK and c-Jun phosphorylation (Fig. 6E, S6D,E) suggesting that Akt may provide a link between RIP1 and JNK activation. Importantly, inhibition of Akt only inhibited the delayed, but not the early, increase in bFGF/zVAD.fmk induced JNK and c-Jun phosphorylation (Fig. S6F). Knockdown of mTOR, rapamycin and the p70S6K inhibitor PF-4708671 also attenuated the necroptosis-associated increase in JNK and c-Jun phosphorylation (Fig. 6F, S6E,G, Fig. S5D). Overall, these data suggested that the Akt-mTORC1-S6K axis, acting downstream from RIP1 kinase, is required for the increase in JNK activity during necroptosis in L929 cells."}

{"project":"GO-BP","denotations":[{"id":"T11919","span":{"begin":793,"end":808},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T11918","span":{"begin":631,"end":646},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T11917","span":{"begin":400,"end":415},"obj":"http://purl.obolibrary.org/obo/GO_0016310"},{"id":"T11916","span":{"begin":44,"end":53},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T11915","span":{"begin":985,"end":996},"obj":"http://purl.obolibrary.org/obo/GO_0097528"},{"id":"T11914","span":{"begin":744,"end":755},"obj":"http://purl.obolibrary.org/obo/GO_0097528"},{"id":"T11913","span":{"begin":352,"end":363},"obj":"http://purl.obolibrary.org/obo/GO_0097528"},{"id":"T11912","span":{"begin":251,"end":262},"obj":"http://purl.obolibrary.org/obo/GO_0097528"},{"id":"T11910","span":{"begin":985,"end":996},"obj":"http://purl.obolibrary.org/obo/GO_0070266"},{"id":"T11909","span":{"begin":744,"end":755},"obj":"http://purl.obolibrary.org/obo/GO_0070266"},{"id":"T11908","span":{"begin":352,"end":363},"obj":"http://purl.obolibrary.org/obo/GO_0070266"},{"id":"T11907","span":{"begin":251,"end":262},"obj":"http://purl.obolibrary.org/obo/GO_0070266"},{"id":"T11905","span":{"begin":965,"end":968},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11904","span":{"begin":779,"end":782},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11903","span":{"begin":617,"end":620},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11902","span":{"begin":489,"end":492},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11901","span":{"begin":386,"end":389},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11900","span":{"begin":240,"end":243},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11899","span":{"begin":0,"end":3},"obj":"http://purl.obolibrary.org/obo/GO_0004705"}],"text":"JNK is a well-established regulator of TNFα synthesis in a variety of systems [13], [14], [15], [34]. Therefore, the ability of Akt and mTORC1 inhibitors to block the increase in TNFα mRNA lead us to examine their role in the activation of JNK during necroptosis. Knockdown of Akt isoforms Akt1 and Akt2 or inhibition of Akt prominently suppressed the necroptosis dependent increase in JNK and c-Jun phosphorylation (Fig. 6E, S6D,E) suggesting that Akt may provide a link between RIP1 and JNK activation. Importantly, inhibition of Akt only inhibited the delayed, but not the early, increase in bFGF/zVAD.fmk induced JNK and c-Jun phosphorylation (Fig. S6F). Knockdown of mTOR, rapamycin and the p70S6K inhibitor PF-4708671 also attenuated the necroptosis-associated increase in JNK and c-Jun phosphorylation (Fig. 6F, S6E,G, Fig. S5D). Overall, these data suggested that the Akt-mTORC1-S6K axis, acting downstream from RIP1 kinase, is required for the increase in JNK activity during necroptosis in L929 cells."}

{"project":"GO-MF","denotations":[{"id":"T11922","span":{"begin":240,"end":243},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11921","span":{"begin":0,"end":3},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11927","span":{"begin":965,"end":968},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11926","span":{"begin":779,"end":782},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11925","span":{"begin":617,"end":620},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11924","span":{"begin":489,"end":492},"obj":"http://purl.obolibrary.org/obo/GO_0004705"},{"id":"T11923","span":{"begin":386,"end":389},"obj":"http://purl.obolibrary.org/obo/GO_0004705"}],"text":"JNK is a well-established regulator of TNFα synthesis in a variety of systems [13], [14], [15], [34]. Therefore, the ability of Akt and mTORC1 inhibitors to block the increase in TNFα mRNA lead us to examine their role in the activation of JNK during necroptosis. Knockdown of Akt isoforms Akt1 and Akt2 or inhibition of Akt prominently suppressed the necroptosis dependent increase in JNK and c-Jun phosphorylation (Fig. 6E, S6D,E) suggesting that Akt may provide a link between RIP1 and JNK activation. Importantly, inhibition of Akt only inhibited the delayed, but not the early, increase in bFGF/zVAD.fmk induced JNK and c-Jun phosphorylation (Fig. S6F). Knockdown of mTOR, rapamycin and the p70S6K inhibitor PF-4708671 also attenuated the necroptosis-associated increase in JNK and c-Jun phosphorylation (Fig. 6F, S6E,G, Fig. S5D). Overall, these data suggested that the Akt-mTORC1-S6K axis, acting downstream from RIP1 kinase, is required for the increase in JNK activity during necroptosis in L929 cells."}

{"project":"GO-CC","denotations":[{"id":"T11931","span":{"begin":1005,"end":1010},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T11930","span":{"begin":880,"end":886},"obj":"http://purl.obolibrary.org/obo/GO_0031931"},{"id":"T11929","span":{"begin":136,"end":142},"obj":"http://purl.obolibrary.org/obo/GO_0031931"}],"text":"JNK is a well-established regulator of TNFα synthesis in a variety of systems [13], [14], [15], [34]. Therefore, the ability of Akt and mTORC1 inhibitors to block the increase in TNFα mRNA lead us to examine their role in the activation of JNK during necroptosis. Knockdown of Akt isoforms Akt1 and Akt2 or inhibition of Akt prominently suppressed the necroptosis dependent increase in JNK and c-Jun phosphorylation (Fig. 6E, S6D,E) suggesting that Akt may provide a link between RIP1 and JNK activation. Importantly, inhibition of Akt only inhibited the delayed, but not the early, increase in bFGF/zVAD.fmk induced JNK and c-Jun phosphorylation (Fig. S6F). Knockdown of mTOR, rapamycin and the p70S6K inhibitor PF-4708671 also attenuated the necroptosis-associated increase in JNK and c-Jun phosphorylation (Fig. 6F, S6E,G, Fig. S5D). Overall, these data suggested that the Akt-mTORC1-S6K axis, acting downstream from RIP1 kinase, is required for the increase in JNK activity during necroptosis in L929 cells."}

{"project":"sentences","denotations":[{"id":"T11858","span":{"begin":837,"end":1011},"obj":"Sentence"},{"id":"T11857","span":{"begin":659,"end":836},"obj":"Sentence"},{"id":"T11856","span":{"begin":505,"end":658},"obj":"Sentence"},{"id":"T11855","span":{"begin":264,"end":504},"obj":"Sentence"},{"id":"T11854","span":{"begin":102,"end":263},"obj":"Sentence"},{"id":"T11853","span":{"begin":0,"end":101},"obj":"Sentence"},{"id":"T164","span":{"begin":0,"end":101},"obj":"Sentence"},{"id":"T165","span":{"begin":102,"end":263},"obj":"Sentence"},{"id":"T166","span":{"begin":264,"end":504},"obj":"Sentence"},{"id":"T167","span":{"begin":505,"end":658},"obj":"Sentence"},{"id":"T168","span":{"begin":659,"end":836},"obj":"Sentence"},{"id":"T169","span":{"begin":837,"end":1011},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"JNK is a well-established regulator of TNFα synthesis in a variety of systems [13], [14], [15], [34]. Therefore, the ability of Akt and mTORC1 inhibitors to block the increase in TNFα mRNA lead us to examine their role in the activation of JNK during necroptosis. Knockdown of Akt isoforms Akt1 and Akt2 or inhibition of Akt prominently suppressed the necroptosis dependent increase in JNK and c-Jun phosphorylation (Fig. 6E, S6D,E) suggesting that Akt may provide a link between RIP1 and JNK activation. Importantly, inhibition of Akt only inhibited the delayed, but not the early, increase in bFGF/zVAD.fmk induced JNK and c-Jun phosphorylation (Fig. S6F). Knockdown of mTOR, rapamycin and the p70S6K inhibitor PF-4708671 also attenuated the necroptosis-associated increase in JNK and c-Jun phosphorylation (Fig. 6F, S6E,G, Fig. S5D). Overall, these data suggested that the Akt-mTORC1-S6K axis, acting downstream from RIP1 kinase, is required for the increase in JNK activity during necroptosis in L929 cells."}

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