PubMed:10228155 JSONTXT

{"project":"PMID_GLOBAL","denotations":[{"id":"T1","span":{"begin":285,"end":311},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T2","span":{"begin":318,"end":323},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T3","span":{"begin":378,"end":387},"obj":"DiseaseOrPhenotypicFeature"},{"id":"T4","span":{"begin":1590,"end":1595},"obj":"DiseaseOrPhenotypicFeature"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"0021055"},{"id":"A2","pred":"mondo_id","subj":"T2","obj":"0005070"},{"id":"A3","pred":"mondo_id","subj":"T3","obj":"0005070"},{"id":"A4","pred":"mondo_id","subj":"T4","obj":"0005070"}],"text":"An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin.\nbeta-catenin plays an essential role in the Wingless/Wnt signaling cascade and is a component of the cadherin cell adhesion complex. Deregulation of beta-catenin accumulation as a result of mutations in adenomatous polyposis coli (APC) tumor suppressor protein is believed to initiate colorectal neoplasia. beta-catenin levels are regulated by the ubiquitin-dependent proteolysis system and beta-catenin ubiquitination is preceded by phosphorylation of its N-terminal region by the glycogen synthase kinase-3beta (GSK-3beta)/Axin kinase complex. Here we show that FWD1 (the mouse homologue of Slimb/betaTrCP), an F-box/WD40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, Axin, GSK-3beta and APC. Mutations at the signal-induced phosphorylation site of beta-catenin inhibited its association with FWD1. FWD1 facilitated ubiquitination and promoted degradation of beta-catenin, resulting in reduced cytoplasmic beta-catenin levels. In contrast, a dominant-negative mutant form of FWD1 inhibited the ubiquitination process and stabilized beta-catenin. These results suggest that the Skp1/Cullin/F-box protein FWD1 (SCFFWD1)-ubiquitin ligase complex is involved in beta-catenin ubiquitination and that FWD1 serves as an intracellular receptor for phosphorylated beta-catenin. FWD1 also links the phosphorylation machinery to the ubiquitin-proteasome pathway to ensure prompt and efficient proteolysis of beta-catenin in response to external signals. SCFFWD1 may be critical for tumor development and suppression through regulation of beta-catenin protein stability."}

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{"project":"2015-BEL-Sample","denotations":[{"id":"T1","span":{"begin":1046,"end":1163},"obj":"cat(p(HGNC:BTRC)) increases deg(p(HGNC:CTNNB1))"}],"text":"An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin.\nbeta-catenin plays an essential role in the Wingless/Wnt signaling cascade and is a component of the cadherin cell adhesion complex. Deregulation of beta-catenin accumulation as a result of mutations in adenomatous polyposis coli (APC) tumor suppressor protein is believed to initiate colorectal neoplasia. beta-catenin levels are regulated by the ubiquitin-dependent proteolysis system and beta-catenin ubiquitination is preceded by phosphorylation of its N-terminal region by the glycogen synthase kinase-3beta (GSK-3beta)/Axin kinase complex. Here we show that FWD1 (the mouse homologue of Slimb/betaTrCP), an F-box/WD40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, Axin, GSK-3beta and APC. Mutations at the signal-induced phosphorylation site of beta-catenin inhibited its association with FWD1. FWD1 facilitated ubiquitination and promoted degradation of beta-catenin, resulting in reduced cytoplasmic beta-catenin levels. In contrast, a dominant-negative mutant form of FWD1 inhibited the ubiquitination process and stabilized beta-catenin. These results suggest that the Skp1/Cullin/F-box protein FWD1 (SCFFWD1)-ubiquitin ligase complex is involved in beta-catenin ubiquitination and that FWD1 serves as an intracellular receptor for phosphorylated beta-catenin. FWD1 also links the phosphorylation machinery to the ubiquitin-proteasome pathway to ensure prompt and efficient proteolysis of beta-catenin in response to external signals. SCFFWD1 may be critical for tumor development and suppression through regulation of beta-catenin protein stability."}

{"project":"2015-BEL-Sample-2","denotations":[{"id":"BEL:20000066","span":{"begin":1046,"end":1163},"obj":"cat(p(HGNC:BTRC)) increases deg(p(HGNC:CTNNB1))"},{"id":"BEL:20033576","span":{"begin":473,"end":626},"obj":"complex(p(HGNC:AXIN1),p(HGNC:GSK3B)) directlyIncreases kin(p(HGNC:GSK3B))"},{"id":"BEL:20033604","span":{"begin":918,"end":1044},"obj":"complex(p(HGNC:BTRC),p(HGNC:CTNNB1)) directlyIncreases deg(p(HGNC:CTNNB1))"},{"id":"BEL:20034092","span":{"begin":812,"end":916},"obj":"complex(p(HGNC:SKP1),p(HGNC:CUL1),p(HGNC:FBXO5),p(HGNC:BTRC)) directlyIncreases complex(p(HGNC:BTRC),p(HGNC:CTNNB1))"},{"id":"BEL:20040698","span":{"begin":918,"end":1044},"obj":"p(HGNC:BTRC) increases deg(p(HGNC:CTNNB1))"},{"id":"BEL:20041244","span":{"begin":812,"end":916},"obj":"p(HGNC:CTNNB1,pmod(P,S)) increases complex(p(HGNC:BTRC),p(HGNC:CTNNB1))"},{"id":"BEL:20041246","span":{"begin":473,"end":626},"obj":"p(HGNC:CTNNB1,pmod(P,S)) directlyIncreases deg(p(HGNC:CTNNB1))"},{"id":"BEL:20029422","span":{"begin":1046,"end":1163},"obj":"cat(p(HGNC:BTRC)) increases deg(p(HGNC:CTNNB1))"},{"id":"BEL:20036696","span":{"begin":473,"end":626},"obj":"kin(p(HGNC:GSK3B)) directlyIncreases p(HGNC:CTNNB1,pmod(P,S))"}],"text":"An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin.\nbeta-catenin plays an essential role in the Wingless/Wnt signaling cascade and is a component of the cadherin cell adhesion complex. Deregulation of beta-catenin accumulation as a result of mutations in adenomatous polyposis coli (APC) tumor suppressor protein is believed to initiate colorectal neoplasia. beta-catenin levels are regulated by the ubiquitin-dependent proteolysis system and beta-catenin ubiquitination is preceded by phosphorylation of its N-terminal region by the glycogen synthase kinase-3beta (GSK-3beta)/Axin kinase complex. Here we show that FWD1 (the mouse homologue of Slimb/betaTrCP), an F-box/WD40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, Axin, GSK-3beta and APC. Mutations at the signal-induced phosphorylation site of beta-catenin inhibited its association with FWD1. FWD1 facilitated ubiquitination and promoted degradation of beta-catenin, resulting in reduced cytoplasmic beta-catenin levels. In contrast, a dominant-negative mutant form of FWD1 inhibited the ubiquitination process and stabilized beta-catenin. These results suggest that the Skp1/Cullin/F-box protein FWD1 (SCFFWD1)-ubiquitin ligase complex is involved in beta-catenin ubiquitination and that FWD1 serves as an intracellular receptor for phosphorylated beta-catenin. FWD1 also links the phosphorylation machinery to the ubiquitin-proteasome pathway to ensure prompt and efficient proteolysis of beta-catenin in response to external signals. SCFFWD1 may be critical for tumor development and suppression through regulation of beta-catenin protein stability."}

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":318,"end":323},"obj":"HP_0002664"},{"id":"T2","span":{"begin":378,"end":387},"obj":"HP_0002664"},{"id":"T3","span":{"begin":1590,"end":1595},"obj":"HP_0002664"}],"text":"An F-box protein, FWD1, mediates ubiquitin-dependent proteolysis of beta-catenin.\nbeta-catenin plays an essential role in the Wingless/Wnt signaling cascade and is a component of the cadherin cell adhesion complex. Deregulation of beta-catenin accumulation as a result of mutations in adenomatous polyposis coli (APC) tumor suppressor protein is believed to initiate colorectal neoplasia. beta-catenin levels are regulated by the ubiquitin-dependent proteolysis system and beta-catenin ubiquitination is preceded by phosphorylation of its N-terminal region by the glycogen synthase kinase-3beta (GSK-3beta)/Axin kinase complex. Here we show that FWD1 (the mouse homologue of Slimb/betaTrCP), an F-box/WD40-repeat protein, specifically formed a multi-molecular complex with beta-catenin, Axin, GSK-3beta and APC. Mutations at the signal-induced phosphorylation site of beta-catenin inhibited its association with FWD1. FWD1 facilitated ubiquitination and promoted degradation of beta-catenin, resulting in reduced cytoplasmic beta-catenin levels. In contrast, a dominant-negative mutant form of FWD1 inhibited the ubiquitination process and stabilized beta-catenin. These results suggest that the Skp1/Cullin/F-box protein FWD1 (SCFFWD1)-ubiquitin ligase complex is involved in beta-catenin ubiquitination and that FWD1 serves as an intracellular receptor for phosphorylated beta-catenin. FWD1 also links the phosphorylation machinery to the ubiquitin-proteasome pathway to ensure prompt and efficient proteolysis of beta-catenin in response to external signals. SCFFWD1 may be critical for tumor development and suppression through regulation of beta-catenin protein stability."}