Article

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.

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.
Journal of Biological Chemistry (impact factor: 4.77). 08/2005; 280(30):27783-91. DOI:10.1074/jbc.M504909200 pp.27783-91
Source: PubMed

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.

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Keywords

conserved protein-protein interaction motif
 
dominant-negative form
 
E-selectin gene
 
E-selectin genes
 
enhanced NF-kappaB-mediated transcription
 
HeLa cells
 
human immunodeficiency virus-1
 
IkappaB alpha
 
molecular interaction
 
NF-kappaB-mediated transcription
 
NF-kappaB-responsive gene transcription
 
nuclear localization
 
nuclear localization sequence
 
nuclear localization sequence polypeptide
 
p65 subunit
 
repressed NF-kappaB-mediated transcription
 
short transcripts
 
stressful conditions
 
transcription enhancement
 
vitro protein-protein interaction assays