NF-kappa B controls expression of inhibitor I kappa B alpha: evidence for an inducible autoregulatory pathway.
The eukaryotic transcription factor nuclear factor-kappa B (NF-kappa B) participates in many parts of the genetic program mediating T lymphocyte activation and growth. Nuclear expression of NF-kappa B occurs after its induced dissociation from its cytoplasmic inhibitor I kappa B alpha. Phorbol ester and tumor necrosis factor-alpha induction of nuclear NF-kappa B is associated with both the degradation of performed I kappa B alpha and the activation of I kappa B alpha gene expression. Transfection studies indicate that the I kappa B alpha gene is specifically induced by the 65-kilodalton transactivating subunit of NF-kappa B. Association of the newly synthesized I kappa B alpha with p65 restores intracellular inhibition of NF-kappa B DNA binding activity and prolongs the survival of this labile inhibitor. Together, these results show that NF-kappa B controls the expression of I kappa B alpha by means of an inducible autoregulatory pathway.
Sun
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SC
Gladstone Institute of Virology and Immunology, University of California, San Francisco.
Ganchi
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PA
Ballard
D W
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Greene
W C
WC
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D020672:I-kappa B Proteins; D015151:Immunoblotting; D007700:Kinetics; D008970:Molecular Weight; D016296:Mutagenesis; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015534:Trans-Activators / Q000494:pharmacology; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D004268:DNA-Binding Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D003513:Cycloheximide; D013755:Tetradecanoylphorbol Acetate