FBI-1 enhances transcription of the nuclear factor-κB (NF-κB)-responsive E-selectin gene by nuclear localization of the p65 subunit of NF-κB

Dong Kee Lee, Jae Eun Kang, Hye Jin Park, Myung Hwa Kim, Tae Hee Yim, Jung Min Kim, Min Kyu Heo, Kyu Yeun Kim, Ho Jeong Kwon, Man Wook Hur

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Abstract

The POZ domain is a highly conserved protein-protein interaction motif found in many regulatory proteins. Nuclear factor-κB (NF-κB) plays a key role in the expression of a variety of genes in response to infection, inflammation, and stressful conditions. We found that the POZ domain of FBI-1 (factor that binds to the inducer of short transcripts of human immunodeficiency virus-1) interacted with the Rel homology domain of the p65 subunit of NF-κB in both in vivo and in vitro protein-protein interaction assays. FBI-1 enhanced NF-κB-mediated transcription of E-selectin genes in HeLa cells upon phorbol 12-myristate 13-acetate stimulation and overcame gene repression by IκBα or IκBβ. In contrast, the POZ domain of FBI-1, which is a dominant-negative form of FBI-1, repressed NF-κB-mediated transcription, and the repression was cooperative with IκBα or IκBβ. In contrast, the POZ domain tagged with a nuclear localization sequence polypeptide of FBI-1 enhanced NF-κB- responsive gene transcription, suggesting that the molecular interaction between the POZ domain and the Rel homology domain of p65 and the nuclear localization by the nuclear localization sequence are important in the transcription enhancement mediated by FBI-1. Confocal microscopy showed that FBI-1 increased NF-κB movement into the nucleus and increased the stability of NF-κB in the nucleus, which enhanced NF-κ-mediated transcription of the E-selectin gene. FBI-1 also interacted with IκBα and IκBβ.

Original languageEnglish
Pages (from-to)27783-27791
Number of pages9
JournalJournal of Biological Chemistry
Volume280
Issue number30
DOIs
Publication statusPublished - 2005 Jul 29

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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