PubMed:9244310 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PubMed/sourceid/9244310","sourcedb":"PubMed","sourceid":"9244310","source_url":"http://www.ncbi.nlm.nih.gov/pubmed/9244310","text":"Identification and characterization of an IkappaB kinase.\nActivation of the transcription factor NF-kappaB by tumor necrosis factor (TNF) and interleukin-1 (IL-1) requires the NF-kappaB-inducing kinase (NIK). In a yeast two-hybrid screen for NIK-interacting proteins, we have identified a protein kinase previously known as CHUK. Overexpression of CHUK activates a NF-kappaB-dependent reporter gene. A catalytically inactive mutant of CHUK is a dominant-negative inhibitor of TNF-, IL-1-, TRAF-, and NIK-induced NF-kappaB activation. CHUK associates with the NF-kappaB inhibitory protein, IkappaB-alpha, in mammalian cells. CHUK specifically phosphorylates IkappaB-alpha on both serine 32 and serine 36, modifications that are required for targeted degradation of IkappaB-alpha via the ubiquitin-proteasome pathway. This phosphorylation of IkappaB-alpha is greatly enhanced by NIK costimulation. Thus, CHUK is a NIK-activated IkappaB-alpha kinase that links TNF- and IL-1-induced kinase cascades to NF-kappaB activation.","tracks":[{"project":"2015-BEL-Sample-2","denotations":[{"id":"BEL:20003606","span":{"begin":624,"end":813},"obj":"p(HGNC:NFKBIA,pmod(P,S)) directlyIncreases deg(p(HGNC:NFKBIA))"}],"attributes":[{"subj":"BEL:20003606","pred":"source","obj":"2015-BEL-Sample-2"}]},{"project":"mondo_disease","denotations":[{"id":"T1","span":{"begin":110,"end":115},"obj":"Disease"}],"attributes":[{"id":"A1","pred":"mondo_id","subj":"T1","obj":"http://purl.obolibrary.org/obo/MONDO_0005070"},{"subj":"T1","pred":"source","obj":"mondo_disease"}]},{"project":"HP-phenotype","denotations":[{"id":"T1","span":{"begin":110,"end":115},"obj":"Phenotype"}],"attributes":[{"id":"A1","pred":"hp_id","subj":"T1","obj":"HP:0002664"},{"subj":"T1","pred":"source","obj":"HP-phenotype"}],"namespaces":[{"prefix":"HP","uri":"http://purl.obolibrary.org/obo/HP_"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2015-BEL-Sample-2","color":"#93ec9e","default":true},{"id":"mondo_disease","color":"#ec93a1"},{"id":"HP-phenotype","color":"#93bbec"}]}]}}