Mutual regulation of the transcriptional activator NF-kappa B and its inhibitor, I kappa B-alpha.

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阅读量：

120

作者：

K Brown，S Park，T Kanno，G Franzoso，U Siebenlist

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摘要：

The NF-κB transcription factor complex is sequestered in the cytoplasm by the inhibitory protein IκB-α (MAD-3). Various cellular stimuli relieve this inhibition by mechanisms largely unknown, leading to NF-κB nuclear localization and transactivation of its target genes. It is demonstrated here with human T lymphocytes and monocytes that different stimuli, including tumor necrosis factor α and phorbol 12-myristate 13-acetate, cause rapid degradation of IκB-α, with concomitant activation of NF-κB, followed by a dramatic increase in IκB-α mRNA and protein synthesis. Transfection studies reveal that the IκB-α mRNA and the encoded protein are potently induced by NF-κB and by homodimers of p65 and of c-Rel. We propose a model in which NF-κB and IκB-α mutually regulate each other in a cycle: saturating amounts of the inhibitory IκB-α protein are destroyed upon stimulation, allowing rapid activation of NF-κB. Subsequently, IκB-α mRNA and protein levels are quickly induced by the activated NF-κB. This resurgence of IκB-α protein acts to restore an equilibrium in which NF-κB is again inhibited.

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关键词：

Immunology Gene Regulation Cell Activation Human Immunodeficiency Virus Transcription Factor Nuclear Translocation

DOI：

10.1073/pnas.90.6.2532

被引量：

2125

年份：

1993