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The mammalian transcriptional repressor RBP (CBF1) regulates interleukin-6 gene expression
C Kannabiran1, X Zeng, L D Vales
1Department of Biochemistry, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway 08854-5635, USA.
Molecular and Cellular Biology
|January 1, 1997
Summary
The mammalian transcriptional repressor RBP inhibits interleukin-6 (IL-6) gene activation. RBP
Area of Science:
- Molecular Biology
- Gene Regulation
- Immunology
Background:
- Interleukin-6 (IL-6) is a key cytokine involved in immune responses and inflammation.
- The IL-6 gene promoter contains an interleukin response element (ILRE) crucial for its activation.
- Nuclear factor-kappa B (NF-kappa B) is a primary transcription factor that binds to the ILRE to activate IL-6 transcription.
Purpose of the Study:
- To investigate the role of the mammalian transcriptional repressor RBP in regulating IL-6 gene expression.
- To determine if RBP can modulate IL-6 transcription mediated by NF-kappa B.
Main Methods:
- Transient-expression assays were employed to assess the effect of RBP on IL-6 gene transcription.
- Analysis of RBP binding site within the ILRE and its impact on RBP-mediated repression.
- Investigating the requirement of NF-kappa B binding for RBP-mediated repression.
Main Results:
- RBP was demonstrated to repress activated transcription of the IL-6 gene.
- The presence and specific location of the RBP target site within the ILRE are essential for repression.
- While RBP binds to the ILRE, it does not target NF-kappa B directly, but NF-kappa B binding is necessary for repression.
Conclusions:
- RBP acts as a transcriptional repressor of the IL-6 gene.
- RBP-mediated repression of IL-6 involves the ILRE and requires NF-kappa B binding.
- RBP inhibits the coactivation of IL-6 transcription by NF-kappa B and C/EBP-beta.