Differential Activation of a C/EBP Isoform by a Novel Redox Switch May Confer the Lipopolysaccharide-inducible Expression of Interleukin-6 Gene
Date Issued
2004-05-27
Date
2004-05-27
Author(s)
呂勝春
DOI
922320B002188
Abstract
C/EBPβ, a member of the CCAAT/enhancer binding
protein (C/EBP) family, is one of the key transcription
factors responsible for the induction of a wide array of
genes, some of which play important roles in innate
immunity, inflammatory response, adipocyte and myeloid
cell differentiation, and the acute phase response.
Three C/EBPβ isoforms (i.e. LAP*, LAP, and LIP) were
known to arise from differential translation initiation
and display different functions in gene regulation.
C/EBPβ is known to induce interleukin (IL)-6 gene when
P388D1 cells are treated with lipopolysaccharide (LPS).
Exactly how the transcriptional activities of C/EBPβ isoforms
are involved in the regulation of the IL-6 gene
remains unclear. Here we report that LPS-induced expression
of IL-6 gene in P388D1 cells is mediated by a
redox switch-activated LAP*. The intramolecular disulfide
bonds of LAP* and LAP have been determined.
Among the cysteine residues, amino acid 11 (Cys11) of
LAP* plays key roles for determining the overall intramolecular
disulfide bonds that form the basis for redox
switch regulation. The DNA binding activity and
transcriptional activity of LAP* are enhanced under reducing
condition. LAP and LIP, lacking 21 and 151
amino acids, respectively, in the N-terminal region, are
not regulated in a similar redox-responsive manner. Our
results indicate that LAP* is the primary isoform of
C/EBPβ that regulates, through a redox switch, the LPSinduced
expression of the IL-6 gene.
Publisher
臺北市：國立臺灣大學醫學院分子醫學研究所
Type
journal article
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