PubMed:23632891 JSON TXT

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DisGeNET5_gene_disease

DisGeNET

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":19,"end":25},"obj":"gene:84433"},{"id":"T1","span":{"begin":106,"end":135},"obj":"disease:C0079744"},{"id":"T2","span":{"begin":86,"end":91},"obj":"gene:4790"},{"id":"T3","span":{"begin":106,"end":135},"obj":"disease:C0079744"},{"id":"T4","span":{"begin":592,"end":597},"obj":"gene:4790"},{"id":"T5","span":{"begin":491,"end":496},"obj":"disease:C0079744"},{"id":"T6","span":{"begin":474,"end":479},"obj":"gene:4790"},{"id":"T7","span":{"begin":491,"end":496},"obj":"disease:C0079744"},{"id":"T8","span":{"begin":655,"end":659},"obj":"gene:2768"},{"id":"T9","span":{"begin":491,"end":496},"obj":"disease:C0079744"},{"id":"T10","span":{"begin":759,"end":764},"obj":"gene:7189"},{"id":"T11","span":{"begin":491,"end":496},"obj":"disease:C0079744"}],"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"},{"id":"R4","pred":"associated_with","subj":"T6","obj":"T7"},{"id":"R5","pred":"associated_with","subj":"T8","obj":"T9"},{"id":"R6","pred":"associated_with","subj":"T10","obj":"T11"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"Trimeric G protein-CARMA1 axis links smoothened, the hedgehog receptor transducer, to NF-κB activation in diffuse large B-cell lymphoma.\nDiffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Aberrant activation of Hedgehog (Hh) and nuclear factor (NF)-κB pathways is ubiquitously observed and known to mediate tumor growth, survival, and chemoresistance in DLBCL. Here, we find that activation of Hh signaling is positively correlated with NF-κB pathway in DLBCL tumors, and that smoothened (SMO), the signal transducer subunit of Hh pathway, contributes to NF-κB activation through recruiting G protein subunits Gαi and Gα12 to activate PKCβ/CARMA1/TRAF6/NEMO signaling axis followed by assembling of the CARMA1/BCL10/MALT1/TRAF6 complex to SMO. Moreover, functional inhibition of SMO enhances the cytotoxic effects of NF-κB inhibitor. Altogether, our study reveals a noncanonical Hh signaling pathway in which SMO activates trimeric G proteins and CARMA1-associated signaling complex, leading to NF-κB activation. This signaling cascade contributes to the survival of DLBCL and may serve as a potential target for combination therapies in DLBCL."}

Allie

{"project":"Allie","denotations":[{"id":"SS1_23632891_1_0","span":{"begin":137,"end":166},"obj":"expanded"},{"id":"SS2_23632891_1_0","span":{"begin":168,"end":173},"obj":"abbr"},{"id":"SS1_23632891_2_0","span":{"begin":248,"end":256},"obj":"expanded"},{"id":"SS2_23632891_2_0","span":{"begin":258,"end":260},"obj":"abbr"},{"id":"SS1_23632891_2_1","span":{"begin":266,"end":280},"obj":"expanded"},{"id":"SS2_23632891_2_1","span":{"begin":282,"end":284},"obj":"abbr"},{"id":"SS1_23632891_3_0","span":{"begin":514,"end":524},"obj":"expanded"},{"id":"SS2_23632891_3_0","span":{"begin":526,"end":529},"obj":"abbr"}],"relations":[{"id":"AE1_23632891_1_0","pred":"abbreviatedTo","subj":"SS1_23632891_1_0","obj":"SS2_23632891_1_0"},{"id":"AE1_23632891_2_0","pred":"abbreviatedTo","subj":"SS1_23632891_2_0","obj":"SS2_23632891_2_0"},{"id":"AE1_23632891_2_1","pred":"abbreviatedTo","subj":"SS1_23632891_2_1","obj":"SS2_23632891_2_1"},{"id":"AE1_23632891_3_0","pred":"abbreviatedTo","subj":"SS1_23632891_3_0","obj":"SS2_23632891_3_0"}],"text":"Trimeric G protein-CARMA1 axis links smoothened, the hedgehog receptor transducer, to NF-κB activation in diffuse large B-cell lymphoma.\nDiffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Aberrant activation of Hedgehog (Hh) and nuclear factor (NF)-κB pathways is ubiquitously observed and known to mediate tumor growth, survival, and chemoresistance in DLBCL. Here, we find that activation of Hh signaling is positively correlated with NF-κB pathway in DLBCL tumors, and that smoothened (SMO), the signal transducer subunit of Hh pathway, contributes to NF-κB activation through recruiting G protein subunits Gαi and Gα12 to activate PKCβ/CARMA1/TRAF6/NEMO signaling axis followed by assembling of the CARMA1/BCL10/MALT1/TRAF6 complex to SMO. Moreover, functional inhibition of SMO enhances the cytotoxic effects of NF-κB inhibitor. Altogether, our study reveals a noncanonical Hh signaling pathway in which SMO activates trimeric G proteins and CARMA1-associated signaling complex, leading to NF-κB activation. This signaling cascade contributes to the survival of DLBCL and may serve as a potential target for combination therapies in DLBCL."}

PubmedHPO

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":151,"end":166},"obj":"HP_0012191"},{"id":"T2","span":{"begin":158,"end":166},"obj":"HP_0002665"},{"id":"T3","span":{"begin":344,"end":349},"obj":"HP_0002664"},{"id":"T4","span":{"begin":497,"end":503},"obj":"HP_0002664"}],"text":"Trimeric G protein-CARMA1 axis links smoothened, the hedgehog receptor transducer, to NF-κB activation in diffuse large B-cell lymphoma.\nDiffuse large B-cell lymphoma (DLBCL) is the most common lymphoid malignancy in adults. Aberrant activation of Hedgehog (Hh) and nuclear factor (NF)-κB pathways is ubiquitously observed and known to mediate tumor growth, survival, and chemoresistance in DLBCL. Here, we find that activation of Hh signaling is positively correlated with NF-κB pathway in DLBCL tumors, and that smoothened (SMO), the signal transducer subunit of Hh pathway, contributes to NF-κB activation through recruiting G protein subunits Gαi and Gα12 to activate PKCβ/CARMA1/TRAF6/NEMO signaling axis followed by assembling of the CARMA1/BCL10/MALT1/TRAF6 complex to SMO. Moreover, functional inhibition of SMO enhances the cytotoxic effects of NF-κB inhibitor. Altogether, our study reveals a noncanonical Hh signaling pathway in which SMO activates trimeric G proteins and CARMA1-associated signaling complex, leading to NF-κB activation. This signaling cascade contributes to the survival of DLBCL and may serve as a potential target for combination therapies in DLBCL."}

PubMed:23632891 JSONTXT

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DisGeNET5_gene_disease

DisGeNET

Allie

PubmedHPO

PubMed:23632891 JSON TXT