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J Biol Chem, Vol. 274, Issue 1, 376-383, January 1, 1999
B
Nuclear Translocation
From the Haemostasis and Thrombosis Research Centre, University
Hospital Leiden, Leiden, 2300 RC The Netherlands
Tissue Factor (TF) gene expression is transiently
induced in human monocytic THP-1 cells by lipopolysaccharide (LPS). We
characterized the transcription factor complexes binding to the TF gene
promoter LPS response element (LRE) (
220 to 172), which contains
binding sites for nuclear factor 
B (NFB) and activator protein 1 (AP1) transcription factors, and examined the nature of the activation of these factors during a 24-h time course of LPS stimulation. We found
proteolysis of the cytoplasmic inhibitory protein IB
and nuclear
translocation of the NFB/Rel family proteins p65 and c-Rel,
corresponding to the transient binding of a p65/c-Rel heterodimer to
the B-like site of the LRE. AP1 binding to the LRE was found to be
constitutive, with the majority of the AP1 complexes being JunD/Fra-2
heterodimers. A change in the activation state of the AP1 complexes
was, however, found to be transient, as determined by JunD
phosphorylation of AP1 bound to the proximal binding site. This
directly correlates to the transient activation of Jun N-terminal
kinase (SAPK/JNK). These data indicate that LPS induction of TF gene
expression in monocytic THP-1 cells is regulated by both the transient
phosphorylation of Jun-family proteins and the nuclear translocation
and transient binding of NFB/Rel proteins.
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