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Brief Communication
Nature Cell Biology  7, 921 - 923 (2005)
Published online: 1 September 2005; | doi:10.1038/ncb1296

Distinct roles of IkappaB proteins in regulating constitutive NF-kappaB activity

Vinay Tergaonkar1, 2, Ricardo G Correa1, Masahito Ikawa3 & Inder M Verma1

1  Laboratory of Genetics, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.

2  Present address: Institute of Molecular and Cell Biology, 61 Biopolis Drive, 138673, Singapore.

3  Present address: Genome information Research Center, Osaka University, 3-1, Osaka 565-0871, Japan.

Correspondence should be addressed to Inder M Verma verma@salk.edu

The inhibitor of NF-kappaB (IkappaB) family of proteins is believed to regulate NF-kappaB activity by cytoplasmic sequestration. We show that in cells depleted of IkappaBalpha, IkappaBbeta and IkappaBepsilon proteins, a small fraction of p65 binds DNA and leads to constitutive activation of NF-kappaB target genes, even without stimulation, whereas most of the p65 remains cytoplasmic. These results indicate that although IkappaBalpha, IkappaBbeta and IkappaBepsilon proteins could be dispensable for cytoplasmic retention of NF-kappaB, they are essential for preventing NF-kappaB-dependent gene expression in the basal state. We also show that in the absence of IkappaBalpha, IkappaBbeta and IkappaBepsilon proteins, cytoplasmic retention of NF-kappaB by other cellular proteins renders the pathway unresponsive to activation.


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Nature Cell Biology
ISSN: 1465-7392
EISSN: 1476-4679
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