Purified human I kappa B can rapidly dissociate the complex of the NF-kappa B transcription factor with its cognate DNA.
I kappa B is an inhibitory protein that stabilizes the inducible cytoplasmic form of the NF-kappa B transcription factor. We have purified I kappa B-alpha, a major form of I kappa B with an apparent molecular size of 37 kd, from cytosol of human placenta. A second chromatographically distinct form, I kappa B-beta, was partially purified and found to be more basic and 3-8 kd larger than the alpha form. The occurrence of distinct forms of I kappa B could explain how NF-kappa B can be activated in response to various agents that signal via different intracellular messenger systems. Both I kappa B-alpha and -beta exclusively inactivated NF-kappa B containing the non-DNA binding 65 kd subunit and, within minutes, could dissociate a high affinity complex of NF-kappa B with its cognate DNA. On the assumption that free I kappa B-alpha and -beta can enter the nucleus, these proteins could rapidly release NF-kappa B from high affinity binding sites in enhancer and promoter elements, thereby terminating NF-kappa B-dependent initiation of gene expression.
Laboratorium für Molekulare Biologie, Ludwig-Maximilians-Universität München, Martinsried, Federal Republic of Germany.
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D002852:Chromatography, Ion Exchange; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D016328:NF-kappa B; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D012097:Repressor Proteins / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA