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jnlpba-st-training

{"project":"jnlpba-st-training","denotations":[{"id":"T1","span":{"begin":0,"end":27},"obj":"protein"},{"id":"T2","span":{"begin":51,"end":71},"obj":"protein"},{"id":"T3","span":{"begin":99,"end":109},"obj":"protein"},{"id":"T4","span":{"begin":155,"end":173},"obj":"protein"},{"id":"T5","span":{"begin":174,"end":194},"obj":"protein"},{"id":"T6","span":{"begin":284,"end":304},"obj":"protein"},{"id":"T7","span":{"begin":305,"end":315},"obj":"protein"},{"id":"T8","span":{"begin":347,"end":376},"obj":"protein"},{"id":"T9","span":{"begin":404,"end":421},"obj":"cell_line"},{"id":"T10","span":{"begin":482,"end":497},"obj":"protein"},{"id":"T11","span":{"begin":537,"end":547},"obj":"protein"},{"id":"T12","span":{"begin":663,"end":673},"obj":"protein"},{"id":"T13","span":{"begin":836,"end":865},"obj":"protein"},{"id":"T14","span":{"begin":923,"end":932},"obj":"cell_line"},{"id":"T15","span":{"begin":1058,"end":1073},"obj":"protein"},{"id":"T16","span":{"begin":1113,"end":1123},"obj":"protein"},{"id":"T17","span":{"begin":1131,"end":1146},"obj":"protein"},{"id":"T18","span":{"begin":1162,"end":1176},"obj":"protein"},{"id":"T19","span":{"begin":1347,"end":1362},"obj":"protein"},{"id":"T20","span":{"begin":1390,"end":1400},"obj":"protein"}],"text":"N- and C-terminal sequences control degradation of MAD3/I kappa B alpha in response to inducers of NF-kappa B activity.\nThe proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B. Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for the endogenous murine protein, exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity, such as phorbol myristate acetate or lipopolysaccharide. In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and, in agreement with previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein. By expressing mutant forms of the human protein in this cell line, we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha. Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation. Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein (residues 32 and 36) and that the mutation of either residue is sufficient to abolish ligand-induced degradation, whereas both residues must be mutated to abolish inducible phosphorylation of the protein. We propose that treatment of 70Z/3 cells with either phorbol myristate acetate or lipopolysaccharide induces a kinase activity which phosphorylates serines 32 and that these phosphorylations target the protein for rapid proteolytic degradation, possibly by the ubiquitin-26S proteasome pathway, thus allowing NF-kappa B to translocate to the nucleus and to activate gene expression."}

pubmed-sentences-benchmark

{"project":"pubmed-sentences-benchmark","denotations":[{"id":"S1","span":{"begin":0,"end":119},"obj":"Sentence"},{"id":"S2","span":{"begin":120,"end":316},"obj":"Sentence"},{"id":"S3","span":{"begin":317,"end":614},"obj":"Sentence"},{"id":"S4","span":{"begin":615,"end":866},"obj":"Sentence"},{"id":"S5","span":{"begin":867,"end":1074},"obj":"Sentence"},{"id":"S6","span":{"begin":1075,"end":1283},"obj":"Sentence"},{"id":"S7","span":{"begin":1284,"end":1620},"obj":"Sentence"},{"id":"S8","span":{"begin":1621,"end":2003},"obj":"Sentence"}],"text":"N- and C-terminal sequences control degradation of MAD3/I kappa B alpha in response to inducers of NF-kappa B activity.\nThe proteolytic degradation of the inhibitory protein MAD3/I kappa B alpha in response to extracellular stimulation is a prerequisite step in the activation of the transcription factor NF-kappa B. Analysis of the expression of human I kappa B alpha protein in stable transfectants of mouse 70Z/3 cells shows that, as for the endogenous murine protein, exogenous I kappa B alpha is degraded in response to inducers of NF-kappa B activity, such as phorbol myristate acetate or lipopolysaccharide. In addition, pretreatment of the cells with the proteasome inhibitor N-Ac-Leu-Leu-norleucinal inhibits this ligand-induced degradation and, in agreement with previous studies, stabilizes a hyperphosphorylated form of the human I kappa B alpha protein. By expressing mutant forms of the human protein in this cell line, we have been able to delineate the sequences responsible for both the ligand-induced phosphorylation and the degradation of I kappa B alpha. Our results show that deletion of the C terminus of the I kappa B alpha molecule up to amino acid 279 abolishes constitutive but not ligand-inducible phosphorylation and inhibits ligand-inducible degradation. Further analysis reveals that the inducible phosphorylation of I kappa B alpha maps to two serines in the N terminus of the protein (residues 32 and 36) and that the mutation of either residue is sufficient to abolish ligand-induced degradation, whereas both residues must be mutated to abolish inducible phosphorylation of the protein. We propose that treatment of 70Z/3 cells with either phorbol myristate acetate or lipopolysaccharide induces a kinase activity which phosphorylates serines 32 and that these phosphorylations target the protein for rapid proteolytic degradation, possibly by the ubiquitin-26S proteasome pathway, thus allowing NF-kappa B to translocate to the nucleus and to activate gene expression."}

genia-medco-coref

GENIAcorpus

PubMed:7565683 JSONTXT

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jnlpba-st-training

pubmed-sentences-benchmark

genia-medco-coref

GENIAcorpus

PubMed:7565683 JSON TXT