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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America. >Functional importance of stripping in NFk beta signaling revealed by a stripping-impaired IkB alpha mutant
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Functional importance of stripping in NFk beta signaling revealed by a stripping-impaired IkB alpha mutant

机译：Functional importance of stripping in NFk beta signaling revealed by a stripping-impaired IkB alpha mutant

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摘要

Stress-response transcription factors such as NFkB turn on hundreds of genes and must have a mechanism for rapid cessation of transcriptional activation. We recently showed that the inhibitor of NFkB signaling, IkB alpha, dramatically accelerates the dissociation of NFkB from transcription sites, a process we have called "stripping." To test the role of the IkB alpha C-terminal PEST (rich in proline, glutamic acid, serine, and threonine residues) sequence in NFkB stripping, a mutant IkB alpha was generated in which five acidic PEST residues were mutated to their neutral analogs. This I.Ba(5xPEST) mutant was impaired in stripping NFkB from DNA and formed a more stable intermediate ternary complex than that formed from IkB alpha(WT) because DNA dissociated more slowly. NMR and amide hydrogen-deuterium exchange mass spectrometry showed that the IkB alpha(5xPEST) appears to be "caught in the act of stripping" because it is not yet completely in the folded and NFkB-bound state. When the mutant was introduced into cells, the rate of postinduction IkB alpha-mediated export of NFkB from the nucleus decreased markedly.

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