PubMed:7739562 JSONTXT

{"project":"jnlpba-st-training","denotations":[{"id":"T1","span":{"begin":14,"end":36},"obj":"protein"},{"id":"T2","span":{"begin":40,"end":55},"obj":"protein"},{"id":"T3","span":{"begin":81,"end":91},"obj":"protein"},{"id":"T4","span":{"begin":108,"end":139},"obj":"protein"},{"id":"T5","span":{"begin":140,"end":150},"obj":"protein"},{"id":"T6","span":{"begin":351,"end":361},"obj":"protein"},{"id":"T7","span":{"begin":422,"end":440},"obj":"protein"},{"id":"T8","span":{"begin":448,"end":463},"obj":"protein"},{"id":"T9","span":{"begin":563,"end":589},"obj":"protein"},{"id":"T10","span":{"begin":601,"end":617},"obj":"protein"},{"id":"T11","span":{"begin":618,"end":643},"obj":"protein"},{"id":"T12","span":{"begin":649,"end":670},"obj":"protein"},{"id":"T13","span":{"begin":683,"end":694},"obj":"protein"},{"id":"T14","span":{"begin":751,"end":766},"obj":"protein"},{"id":"T15","span":{"begin":792,"end":802},"obj":"protein"},{"id":"T16","span":{"begin":845,"end":860},"obj":"protein"},{"id":"T17","span":{"begin":926,"end":945},"obj":"cell_type"},{"id":"T18","span":{"begin":976,"end":1001},"obj":"protein"},{"id":"T19","span":{"begin":1005,"end":1020},"obj":"protein"},{"id":"T20","span":{"begin":1081,"end":1091},"obj":"protein"},{"id":"T21","span":{"begin":1225,"end":1240},"obj":"protein"},{"id":"T22","span":{"begin":1246,"end":1256},"obj":"protein"},{"id":"T23","span":{"begin":1260,"end":1280},"obj":"cell_line"},{"id":"T24","span":{"begin":1361,"end":1389},"obj":"protein"},{"id":"T25","span":{"begin":1393,"end":1408},"obj":"protein"},{"id":"T26","span":{"begin":1464,"end":1467},"obj":"protein"},{"id":"T27","span":{"begin":1544,"end":1554},"obj":"protein"},{"id":"T28","span":{"begin":1597,"end":1627},"obj":"protein"},{"id":"T29","span":{"begin":1843,"end":1864},"obj":"protein"},{"id":"T30","span":{"begin":1942,"end":1957},"obj":"protein"},{"id":"T31","span":{"begin":2012,"end":2027},"obj":"protein"},{"id":"T32","span":{"begin":2032,"end":2042},"obj":"protein"}],"text":"Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation.\nThe eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli."}

{"project":"genia-medco-coref","denotations":[{"id":"C2","span":{"begin":40,"end":55},"obj":"NP"},{"id":"C1","span":{"begin":12,"end":55},"obj":"NP"},{"id":"C3","span":{"begin":104,"end":150},"obj":"NP"},{"id":"C4","span":{"begin":351,"end":361},"obj":"NP"},{"id":"C5","span":{"begin":419,"end":440},"obj":"NP"},{"id":"C6","span":{"begin":448,"end":463},"obj":"NP"},{"id":"C7","span":{"begin":465,"end":491},"obj":"NP"},{"id":"C8","span":{"begin":546,"end":589},"obj":"NP"},{"id":"C9","span":{"begin":745,"end":812},"obj":"NP"},{"id":"C11","span":{"begin":845,"end":860},"obj":"NP"},{"id":"C10","span":{"begin":828,"end":860},"obj":"NP"},{"id":"C12","span":{"begin":861,"end":865},"obj":"NP"},{"id":"C13","span":{"begin":875,"end":878},"obj":"NP"},{"id":"C15","span":{"begin":1005,"end":1020},"obj":"NP"},{"id":"C14","span":{"begin":961,"end":1020},"obj":"NP"},{"id":"C16","span":{"begin":1039,"end":1042},"obj":"NP"},{"id":"C17","span":{"begin":1081,"end":1091},"obj":"NP"},{"id":"C18","span":{"begin":1119,"end":1141},"obj":"NP"},{"id":"C19","span":{"begin":1225,"end":1240},"obj":"NP"},{"id":"C20","span":{"begin":1246,"end":1256},"obj":"NP"},{"id":"C21","span":{"begin":1393,"end":1408},"obj":"NP"},{"id":"C22","span":{"begin":1422,"end":1445},"obj":"NP"},{"id":"C23","span":{"begin":1446,"end":1450},"obj":"NP"},{"id":"C24","span":{"begin":1489,"end":1493},"obj":"NP"},{"id":"C25","span":{"begin":1838,"end":1864},"obj":"NP"},{"id":"C27","span":{"begin":1942,"end":1957},"obj":"NP"},{"id":"C26","span":{"begin":1905,"end":1957},"obj":"NP"},{"id":"C28","span":{"begin":1958,"end":1962},"obj":"NP"},{"id":"C29","span":{"begin":2012,"end":2027},"obj":"NP"},{"id":"C30","span":{"begin":2032,"end":2042},"obj":"NP"}],"relations":[{"id":"R1","pred":"coref-ident","subj":"C4","obj":"C3"},{"id":"R2","pred":"coref-ident","subj":"C5","obj":"C2"},{"id":"R3","pred":"coref-ident","subj":"C6","obj":"C5"},{"id":"R4","pred":"coref-ident","subj":"C7","obj":"C6"},{"id":"R5","pred":"coref-ident","subj":"C9","obj":"C8"},{"id":"R6","pred":"coref-ident","subj":"C11","obj":"C7"},{"id":"R7","pred":"coref-relat","subj":"C12","obj":"C10"},{"id":"R8","pred":"coref-pron","subj":"C13","obj":"C11"},{"id":"R9","pred":"coref-ident","subj":"C15","obj":"C11"},{"id":"R10","pred":"coref-pron","subj":"C16","obj":"C15"},{"id":"R11","pred":"coref-ident","subj":"C17","obj":"C4"},{"id":"R12","pred":"coref-ident","subj":"C18","obj":"C14"},{"id":"R13","pred":"coref-ident","subj":"C19","obj":"C15"},{"id":"R14","pred":"coref-ident","subj":"C20","obj":"C17"},{"id":"R15","pred":"coref-ident","subj":"C21","obj":"C19"},{"id":"R16","pred":"coref-relat","subj":"C23","obj":"C22"},{"id":"R17","pred":"coref-relat","subj":"C24","obj":"C22"},{"id":"R18","pred":"coref-ident","subj":"C25","obj":"C21"},{"id":"R19","pred":"coref-ident","subj":"C27","obj":"C25"},{"id":"R20","pred":"coref-ident","subj":"C26","obj":"C1"},{"id":"R21","pred":"coref-relat","subj":"C28","obj":"C26"},{"id":"R22","pred":"coref-ident","subj":"C29","obj":"C27"},{"id":"R23","pred":"coref-ident","subj":"C30","obj":"C20"}],"text":"Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation.\nThe eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli."}

{"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":103},"obj":"Sentence"},{"id":"S2","span":{"begin":104,"end":326},"obj":"Sentence"},{"id":"S3","span":{"begin":327,"end":464},"obj":"Sentence"},{"id":"S4","span":{"begin":465,"end":733},"obj":"Sentence"},{"id":"S5","span":{"begin":734,"end":946},"obj":"Sentence"},{"id":"S6","span":{"begin":947,"end":1109},"obj":"Sentence"},{"id":"S7","span":{"begin":1110,"end":1281},"obj":"Sentence"},{"id":"S8","span":{"begin":1282,"end":1628},"obj":"Sentence"},{"id":"S9","span":{"begin":1629,"end":1865},"obj":"Sentence"},{"id":"S10","span":{"begin":1866,"end":2083},"obj":"Sentence"}],"text":"Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation.\nThe eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli."}

{"project":"GENIAcorpus","denotations":[{"id":"T1","span":{"begin":14,"end":36},"obj":"protein_domain_or_region"},{"id":"T2","span":{"begin":40,"end":55},"obj":"protein_molecule"},{"id":"T3","span":{"begin":59,"end":76},"obj":"other_name"},{"id":"T4","span":{"begin":81,"end":91},"obj":"protein_molecule"},{"id":"T5","span":{"begin":108,"end":139},"obj":"protein_family_or_group"},{"id":"T6","span":{"begin":140,"end":150},"obj":"protein_molecule"},{"id":"T7","span":{"begin":201,"end":236},"obj":"virus"},{"id":"T8","span":{"begin":290,"end":314},"obj":"other_name"},{"id":"T9","span":{"begin":319,"end":325},"obj":"other_name"},{"id":"T10","span":{"begin":331,"end":347},"obj":"other_name"},{"id":"T11","span":{"begin":351,"end":361},"obj":"protein_molecule"},{"id":"T12","span":{"begin":392,"end":415},"obj":"cell_component"},{"id":"T13","span":{"begin":422,"end":440},"obj":"protein_subunit"},{"id":"T14","span":{"begin":448,"end":463},"obj":"protein_subunit"},{"id":"T15","span":{"begin":563,"end":573},"obj":"protein_molecule"},{"id":"T16","span":{"begin":601,"end":617},"obj":"protein_family_or_group"},{"id":"T17","span":{"begin":618,"end":643},"obj":"protein_family_or_group"},{"id":"T18","span":{"begin":649,"end":670},"obj":"protein_family_or_group"},{"id":"T19","span":{"begin":683,"end":694},"obj":"protein_molecule"},{"id":"T20","span":{"begin":698,"end":732},"obj":"virus"},{"id":"T21","span":{"begin":751,"end":766},"obj":"protein_subunit"},{"id":"T22","span":{"begin":792,"end":802},"obj":"protein_molecule"},{"id":"T23","span":{"begin":845,"end":860},"obj":"protein_molecule"},{"id":"T24","span":{"begin":926,"end":931},"obj":"cell_type"},{"id":"T25","span":{"begin":932,"end":945},"obj":"cell_type"},{"id":"T26","span":{"begin":976,"end":1001},"obj":"protein_domain_or_region"},{"id":"T27","span":{"begin":1005,"end":1020},"obj":"protein_molecule"},{"id":"T28","span":{"begin":1081,"end":1091},"obj":"protein_molecule"},{"id":"T29","span":{"begin":1099,"end":1108},"obj":"cell_component"},{"id":"T30","span":{"begin":1133,"end":1141},"obj":"other_name"},{"id":"T31","span":{"begin":1164,"end":1179},"obj":"other_name"},{"id":"T32","span":{"begin":1181,"end":1197},"obj":"other_name"},{"id":"T33","span":{"begin":1225,"end":1240},"obj":"protein_molecule"},{"id":"T34","span":{"begin":1246,"end":1256},"obj":"protein_molecule"},{"id":"T35","span":{"begin":1260,"end":1263},"obj":"protein_molecule"},{"id":"T36","span":{"begin":1322,"end":1337},"obj":"amino_acid_monomer"},{"id":"T37","span":{"begin":1361,"end":1389},"obj":"protein_domain_or_region"},{"id":"T38","span":{"begin":1393,"end":1408},"obj":"protein_molecule"},{"id":"T39","span":{"begin":1464,"end":1467},"obj":"protein_molecule"},{"id":"T40","span":{"begin":1513,"end":1539},"obj":"other_name"},{"id":"T41","span":{"begin":1544,"end":1554},"obj":"protein_molecule"},{"id":"T42","span":{"begin":1660,"end":1681},"obj":"amino_acid_monomer"},{"id":"T43","span":{"begin":1786,"end":1808},"obj":"other_name"},{"id":"T44","span":{"begin":1813,"end":1834},"obj":"other_name"},{"id":"T45","span":{"begin":1843,"end":1864},"obj":"protein_family_or_group"},{"id":"T46","span":{"begin":1942,"end":1957},"obj":"protein_molecule"},{"id":"T47","span":{"begin":2012,"end":2027},"obj":"protein_molecule"},{"id":"T48","span":{"begin":2032,"end":2042},"obj":"protein_molecule"}],"text":"Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation.\nThe eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli."}

{"project":"bionlp-st-gro-2013-training","denotations":[{"id":"T1","span":{"begin":30,"end":36},"obj":"ProteinDomain"},{"id":"T2","span":{"begin":40,"end":55},"obj":"Protein"},{"id":"T3","span":{"begin":81,"end":91},"obj":"TranscriptionFactor"},{"id":"T5","span":{"begin":108,"end":118},"obj":"Eukaryote"},{"id":"T6","span":{"begin":119,"end":139},"obj":"TranscriptionFactor"},{"id":"T7","span":{"begin":140,"end":150},"obj":"TranscriptionFactor"},{"id":"T10","span":{"begin":201,"end":236},"obj":"Virus"},{"id":"T12","span":{"begin":297,"end":303},"obj":"Cell"},{"id":"T15","span":{"begin":351,"end":361},"obj":"TranscriptionFactor"},{"id":"T17","span":{"begin":392,"end":415},"obj":"CellComponent"},{"id":"T18","span":{"begin":422,"end":440},"obj":"ProteinSubunit"},{"id":"T19","span":{"begin":448,"end":463},"obj":"Protein"},{"id":"T20","span":{"begin":470,"end":481},"obj":"CellComponent"},{"id":"T21","span":{"begin":482,"end":491},"obj":"Protein"},{"id":"T24","span":{"begin":563,"end":573},"obj":"TranscriptionFactor"},{"id":"T26","span":{"begin":583,"end":589},"obj":"Chemical"},{"id":"T27","span":{"begin":601,"end":607},"obj":"Cell"},{"id":"T28","span":{"begin":608,"end":616},"obj":"Chemical"},{"id":"T29","span":{"begin":618,"end":643},"obj":"Protein"},{"id":"T30","span":{"begin":649,"end":654},"obj":"Virus"},{"id":"T31","span":{"begin":655,"end":670},"obj":"TranscriptionActivator"},{"id":"T33","span":{"begin":698,"end":703},"obj":"Eukaryote"},{"id":"T34","span":{"begin":704,"end":710},"obj":"Cell"},{"id":"T35","span":{"begin":711,"end":732},"obj":"Virus"},{"id":"T36","span":{"begin":751,"end":766},"obj":"Protein"},{"id":"T37","span":{"begin":792,"end":802},"obj":"TranscriptionFactor"},{"id":"T39","span":{"begin":834,"end":860},"obj":"MutantProtein"},{"id":"T41","span":{"begin":926,"end":931},"obj":"Eukaryote"},{"id":"T42","span":{"begin":932,"end":945},"obj":"Cell"},{"id":"T43","span":{"begin":990,"end":1001},"obj":"AminoAcid"},{"id":"T44","span":{"begin":1005,"end":1020},"obj":"Protein"},{"id":"T45","span":{"begin":1081,"end":1091},"obj":"TranscriptionFactor"},{"id":"T46","span":{"begin":1099,"end":1108},"obj":"CellComponent"},{"id":"T47","span":{"begin":1124,"end":1141},"obj":"MutatedProtein"},{"id":"T52","span":{"begin":1225,"end":1240},"obj":"Protein"},{"id":"T53","span":{"begin":1246,"end":1256},"obj":"TranscriptionFactor"},{"id":"T54","span":{"begin":1260,"end":1263},"obj":"Protein"},{"id":"T56","span":{"begin":1275,"end":1280},"obj":"Cell"},{"id":"T57","span":{"begin":1361,"end":1389},"obj":"ProteinDomain"},{"id":"T58","span":{"begin":1393,"end":1408},"obj":"Protein"},{"id":"T59","span":{"begin":1435,"end":1445},"obj":"TranscriptionRepressor"},{"id":"T60","span":{"begin":1464,"end":1467},"obj":"Protein"},{"id":"T65","span":{"begin":1544,"end":1554},"obj":"TranscriptionFactor"},{"id":"T68","span":{"begin":1597,"end":1604},"obj":"Chemical"},{"id":"T69","span":{"begin":1609,"end":1627},"obj":"Protein"},{"id":"T73","span":{"begin":1843,"end":1854},"obj":"CellComponent"},{"id":"T74","span":{"begin":1855,"end":1864},"obj":"Protein"},{"id":"T75","span":{"begin":1932,"end":1938},"obj":"ProteinDomain"},{"id":"T76","span":{"begin":1942,"end":1957},"obj":"Protein"},{"id":"T78","span":{"begin":2012,"end":2027},"obj":"Protein"},{"id":"T79","span":{"begin":2032,"end":2042},"obj":"TranscriptionFactor"},{"id":"T80","span":{"begin":2058,"end":2063},"obj":"Virus"},{"id":"T83","span":{"begin":331,"end":338},"obj":"Nucleus"},{"id":"T32","span":{"begin":683,"end":694},"obj":"Protein"},{"id":"E1","span":{"begin":92,"end":102},"obj":"PositiveRegulation"},{"id":"E2","span":{"begin":179,"end":186},"obj":"Increase"},{"id":"E3","span":{"begin":187,"end":197},"obj":"GeneExpression"},{"id":"E4","span":{"begin":280,"end":289},"obj":"RegulatoryProcess"},{"id":"E5","span":{"begin":304,"end":314},"obj":"PositiveRegulation"},{"id":"E6","span":{"begin":319,"end":325},"obj":"CellGrowth"},{"id":"E7","span":{"begin":373,"end":382},"obj":"RegulatoryProcess"},{"id":"E8","span":{"begin":503,"end":517},"obj":"Phosphorylation"},{"id":"E9","span":{"begin":522,"end":530},"obj":"ProteinCatabolism"},{"id":"E10","span":{"begin":574,"end":582},"obj":"PositiveRegulation"},{"id":"E12","span":{"begin":803,"end":812},"obj":"PositiveRegulation"},{"id":"E13","span":{"begin":879,"end":889},"obj":"NegativeRegulation"},{"id":"E14","span":{"begin":1142,"end":1151},"obj":"NegativeRegulation"},{"id":"E15","span":{"begin":1156,"end":1163},"obj":"PositiveRegulation"},{"id":"E16","span":{"begin":1164,"end":1179},"obj":"Phosphorylation"},{"id":"E18","span":{"begin":1264,"end":1274},"obj":"GeneExpression"},{"id":"E19","span":{"begin":1468,"end":1475},"obj":"PositiveRegulation"},{"id":"E20","span":{"begin":1503,"end":1512},"obj":"NegativeRegulation"},{"id":"E21","span":{"begin":1520,"end":1530},"obj":"PositiveRegulation"},{"id":"E22","span":{"begin":1531,"end":1539},"obj":"Pathway"},{"id":"E23","span":{"begin":1555,"end":1564},"obj":"PositiveRegulation"},{"id":"E24","span":{"begin":1582,"end":1591},"obj":"PositiveRegulation"},{"id":"E25","span":{"begin":1642,"end":1654},"obj":"ModificationOfMolecularEntity"},{"id":"E26","span":{"begin":1697,"end":1706},"obj":"RegulatoryProcess"},{"id":"E27","span":{"begin":1786,"end":1801},"obj":"Phosphorylation"},{"id":"E28","span":{"begin":1976,"end":1984},"obj":"RegulatoryProcess"},{"id":"E29","span":{"begin":68,"end":76},"obj":"Pathway"},{"id":"E11","span":{"begin":2046,"end":2054},"obj":"ResponseProcess"},{"id":"E17","span":{"begin":1976,"end":1984},"obj":"RegulatoryProcess"},{"id":"E30","span":{"begin":1582,"end":1591},"obj":"PositiveRegulation"},{"id":"E31","span":{"begin":280,"end":289},"obj":"RegulatoryProcess"}],"relations":[{"id":"R1","pred":"hasPart","subj":"T2","obj":"T1"},{"id":"R2","pred":"fromSpecies","subj":"T7","obj":"T5"},{"id":"R3","pred":"locatedIn","subj":"E5","obj":"T12"},{"id":"R4","pred":"locatedIn","subj":"E6","obj":"T12"},{"id":"R5","pred":"locatedIn","subj":"E7","obj":"T17"},{"id":"R6","pred":"locatedIn","subj":"T21","obj":"T20"},{"id":"R7","pred":"locatedIn","subj":"T28","obj":"T27"},{"id":"R8","pred":"fromSpecies","subj":"T31","obj":"T30"},{"id":"R10","pred":"fromSpecies","subj":"T34","obj":"T33"},{"id":"R11","pred":"locatedIn","subj":"T39","obj":"T42"},{"id":"R12","pred":"locatedIn","subj":"E13","obj":"T42"},{"id":"R13","pred":"fromSpecies","subj":"T42","obj":"T41"},{"id":"R14","pred":"hasPart","subj":"T44","obj":"T43"},{"id":"R16","pred":"locatedIn","subj":"E18","obj":"T56"},{"id":"R17","pred":"hasPart","subj":"T58","obj":"T57"},{"id":"R18","pred":"hasPart","subj":"T76","obj":"T75"},{"id":"R9","pred":"hasPart","subj":"T53","obj":"T52"},{"id":"R11","pred":"hasPatient","subj":"T3","obj":"E1"},{"id":"R12","pred":"hasPatient","subj":"E3","obj":"E2"},{"id":"R13","pred":"hasPatient","subj":"T10","obj":"E3"},{"id":"R14","pred":"hasPatient","subj":"E5","obj":"E4"},{"id":"R15","pred":"hasAgent","subj":"T19","obj":"E7"},{"id":"R16","pred":"hasPatient","subj":"T15","obj":"E7"},{"id":"R17","pred":"hasPatient","subj":"T21","obj":"E8"},{"id":"R18","pred":"hasPatient","subj":"T21","obj":"E9"},{"id":"R19","pred":"hasAgent","subj":"T26","obj":"E10"},{"id":"R20","pred":"hasPatient","subj":"T24","obj":"E10"},{"id":"R21","pred":"hasAgent","subj":"T36","obj":"E12"},{"id":"R22","pred":"hasPatient","subj":"T37","obj":"E12"},{"id":"R23","pred":"hasAgent","subj":"T39","obj":"E13"},{"id":"R24","pred":"hasAgent","subj":"T47","obj":"E14"},{"id":"R25","pred":"hasPatient","subj":"E16","obj":"E14"},{"id":"R26","pred":"hasPatient","subj":"E16","obj":"E15"},{"id":"R27","pred":"hasPatient","subj":"T54","obj":"E18"},{"id":"R28","pred":"hasAgent","subj":"T60","obj":"E19"},{"id":"R29","pred":"hasAgent","subj":"T59","obj":"E20"},{"id":"R30","pred":"hasPatient","subj":"E22","obj":"E20"},{"id":"R31","pred":"hasPatient","subj":"E23","obj":"E22"},{"id":"R32","pred":"hasPatient","subj":"T65","obj":"E23"},{"id":"R33","pred":"hasAgent","subj":"T68","obj":"E24"},{"id":"R34","pred":"hasPatient","subj":"E22","obj":"E24"},{"id":"R35","pred":"hasAgent","subj":"E25","obj":"E26"},{"id":"R36","pred":"hasAgent","subj":"T75","obj":"E28"},{"id":"R37","pred":"hasPatient","subj":"T78","obj":"E28"},{"id":"R38","pred":"hasPatient","subj":"E1","obj":"E29"},{"id":"R39","pred":"hasAgent","subj":"T80","obj":"E11"},{"id":"R40","pred":"hasAgent","subj":"T75","obj":"E17"},{"id":"R41","pred":"hasPatient","subj":"T79","obj":"E17"},{"id":"R42","pred":"hasAgent","subj":"T69","obj":"E30"},{"id":"R43","pred":"hasPatient","subj":"E22","obj":"E30"},{"id":"R44","pred":"hasPatient","subj":"E6","obj":"E31"}],"text":"Coupling of a signal response domain in I kappa B alpha to multiple pathways for NF-kappa B activation.\nThe eukaryotic transcription factor NF-kappa B plays a central role in the induced expression of human immunodeficiency virus type 1 and in many aspects of the genetic program mediating normal T-cell activation and growth. The nuclear activity of NF-kappa B is tightly regulated from the cytoplasmic compartment by an inhibitory subunit called I kappa B alpha. This cytoplasmic inhibitor is rapidly phosphorylated and degraded in response to a diverse set of NF-kappa B-inducing agents, including T-cell mitogens, proinflammatory cytokines, and viral transactivators such as the Tax protein of human T-cell leukemia virus type 1. To explore these I kappa B alpha-dependent mechanisms for NF-kappa B induction, we identified novel mutants of I kappa B alpha that uncouple its inhibitory and signal-transducing functions in human T lymphocytes. Specifically, removal of the N-terminal 36 amino acids of I kappa B alpha failed to disrupt its ability to form latent complexes with NF-kappa B in the cytoplasm. However, this deletion mutation prevented the induced phosphorylation, degradative loss, and functional release of I kappa B alpha from NF-kappa B in Tax-expressing cells. Alanine substitutions introduced at two serine residues positioned within this N-terminal regulatory region of I kappa B alpha also yielded constitutive repressors that escaped from Tax-induced turnover and that potently inhibited immune activation pathways for NF-kappa B induction, including those initiated from antigen and cytokine receptors. In contrast, introduction of a phosphoserine mimetic at these sites rectified this functional defect, a finding consistent with a causal linkage between the phosphorylation status and proteolytic stability of this cytoplasmic inhibitor. Together, these in vivo studies define a critical signal response domain in I kappa B alpha that coordinately controls the biologic activities of I kappa B alpha and NF-kappa B in response to viral and immune stimuli."}