Journal article
Low nuclear levels of nuclear factor-κB are essential for KC self-induction in astrocytes: Requirements for shuttling and phosphorylation
Glia, Vol.48(4), pp.327-336
12/2004
DOI: 10.1002/glia.20087
PMID: 15390109
Abstract
Stimulation with the chemokine KC induces an autocrine response in mouse astrocytes. A requirement for NF-κB was established for KC self-induction. NF-κB inhibitors, p65 antisense oligonucleotides, or dominant-negative IκBα inhibited this autocrine response. Mutation of a specific κB site in the KC promoter also blocked KC self-induction. Chromatin immunoprecipitation and in vivo footprinting confirmed the direct binding of NF-κB to the KC promoter. However, neither NF-κB nuclear translocation, increased IκB degradation, nor upregulation of NF-κB DNA binding activity was observed after KC stimulation. Reporter gene assays demonstrated KC-upregulated NF-κB transcriptional activity, and this effect was inhibited by dominant-negative IκBα. Accumulation of NF-κB was noted within the nucleus in the presence of nuclear export inhibitor leptomycin B, demonstrating constitutive shuttling of NF-κB between the cytoplasm and nucleus. Blocking NF-κB shuttling inhibited KC transcription. KC induced p65 phosphorylation, which was critical for NF-κB activation as determined with the Gal-4-p65 fusion protein and mutation of p65 phosphorylation sites. In conclusion, low-level nuclear NF-κB is essential for KC self-induction, and this effect is mediated by shuttling and phosphorylation of NF-κB. The results outline a novel mechanism for NF-κB participation in transcription regulation. © 2004 Wiley-Liss, Inc.
Details
- Title: Subtitle
- Low nuclear levels of nuclear factor-κB are essential for KC self-induction in astrocytes: Requirements for shuttling and phosphorylation
- Creators
- Qiwei Zhai - Harvard UniversityYi Luo - Harvard UniversityYe Zhang - Harvard UniversityMichael A. Berman - Harvard UniversityMartin E. Dorf - Harvard University
- Resource Type
- Journal article
- Publication Details
- Glia, Vol.48(4), pp.327-336
- Publisher
- Wiley Subscription Services, Inc., A Wiley Company
- DOI
- 10.1002/glia.20087
- PMID
- 15390109
- ISSN
- 0894-1491
- eISSN
- 1098-1136
- Number of pages
- 10
- Language
- English
- Date published
- 12/2004
- Academic Unit
- Urology
- Record Identifier
- 9984319972002771
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