title: FBI-1 enhances transcription of the nuclear factor-kappaB (NF-kappaB)-responsive E-selectin gene by nuclear localization of the p65 subunit of NF-kappaB.
abstract: The POZ domain is a highly conserved protein-protein interaction motif found in many regulatory proteins. Nuclear factor-kappaB (NF-kappaB) 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-kappaB in both in vivo and in vitro protein-protein interaction assays. FBI-1 enhanced NF-kappaB-mediated transcription of E-selectin genes in HeLa cells upon phorbol 12-myristate 13-acetate stimulation and overcame gene repression by IkappaB alpha or IkappaB beta. In contrast, the POZ domain of FBI-1, which is a dominant-negative form of FBI-1, repressed NF-kappaB-mediated transcription, and the repression was cooperative with IkappaB alpha or IkappaB beta. In contrast, the POZ domain tagged with a nuclear localization sequence polypeptide of FBI-1 enhanced NF-kappaB-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-kappaB movement into the nucleus and increased the stability of NF-kappaB in the nucleus, which enhanced NF-kappaB-mediated transcription of the E-selectin gene. FBI-1 also interacted with IkappaB alpha and IkappaB beta.
authors.affiliation: Department of Biochemistry and Molecular Biology and the Institute of Genetic Sciences, BK21 Project for Medical Sciences, Yonsei University School of Medicine, 134 ShinChon-Dong, SeoDaeMoon-Ku, Seoul 120-752, Korea.
authors.forename: Dong-Kee
authors.initials: DK
authors.lastname: Lee
authors.forename: Jae-Eun
authors.initials: JE
authors.lastname: Kang
authors.forename: Hye-Jin
authors.initials: HJ
authors.lastname: Park
authors.forename: Myung-Hwa
authors.initials: MH
authors.lastname: Kim
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Yim
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Min-Kyu
authors.initials: MK
authors.lastname: Heo
authors.forename: Kyu-Yeun
authors.initials: KY
authors.lastname: Kim
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Man-Wook
authors.initials: MW
authors.lastname: Hur
mesh_terms: D021581:Active Transport, Cell Nucleus; D015153:Blotting, Western; D002467:Cell Nucleus / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D019040:E-Selectin / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005799:Genes, Dominant; D006367:HeLa Cells; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015151:Immunoblotting; D047468:Immunoprecipitation; D007976:Leupeptins / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D019040:E-Selectin; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D007976:Leupeptins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D010455:Peptides; D011993:Recombinant Fusion Proteins; D013859:Thiocarbamates; D014157:Transcription Factors; C485514:ZBTB7A protein, human; C066229:prolinedithiocarbamate; D000072000:NF-KappaB Inhibitor alpha; D011392:Proline; D008156:Luciferases; D013755:Tetradecanoylphorbol Acetate; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde