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Publication : Kinetic enhancement of NF-kappaBxDNA dissociation by IkappaBalpha.

First Author  Bergqvist S Year  2009
Journal  Proc Natl Acad Sci U S A Volume  106
Issue  46 Pages  19328-33
PubMed ID  19887633 Mgi Jnum  J:247479
Mgi Id  MGI:5927517 Doi  10.1073/pnas.0908797106
Citation  Bergqvist S, et al. (2009) Kinetic enhancement of NF-kappaBxDNA dissociation by IkappaBalpha. Proc Natl Acad Sci U S A 106(46):19328-33
abstractText  A hallmark of the NF-kappaB transcription response to inflammatory cytokines is the remarkably rapid rate of robust activation and subsequent signal repression. Although the rapidity of postinduction repression is explained partly by the fact that the gene for IkappaBalpha is strongly induced by NF-kappaB, the newly synthesized IkappaBalpha still must enter the nucleus and compete for binding to NF-kappaB with the very large number of kappaB sites in the DNA. We present results from real-time binding kinetic experiments, demonstrating that IkappaBalpha increases the dissociation rate of NF-kappaB from the DNA in a highly efficient kinetic process. Analysis of various IkappaB mutant proteins shows that this process requires the C-terminal PEST sequence and the weakly folded fifth and sixth ankyrin repeats of IkappaBalpha. Mutational stabilization of these repeats reduces the efficiency with which IkappaBalpha enhances the dissociation rate.
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