Details

Autor(en) / Beteiligte

• Su, Wen-Chi
• Chou, Han-Yi
• Chang, Ching-Jin
• Lee, Yu-May
• Chen, Wei-Hao
• Huang, Kuo-Hsiang
• Lee, Ming-Yue
• Lee, Sheng-Chung

Titel

Differential Activation of a C/EBPβ Isoform by a Novel Redox Switch May Confer the Lipopolysaccharide-inducible Expression of Interleukin-6 Gene

Ist Teil von

• The Journal of biological chemistry, 2003-12, Vol.278 (51), p.51150-51158

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 LPS-induced expression of the IL-6 gene.