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Journal article
Evidence for Activation of the TGF-[beta]1 Promoter by C/EBP[beta] and Its Modulation by Smads
Journal of interferon & cytokine research, v 29(1)
01 Jan 2009
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The transforming growth factor-β1 (TGF-β1) is a cytokine involved in many biological events inlcuding immunosuppression, angiogenesis, cell growth, and apoptosis. Expression of TGF-β1 at the transcriptional level is controlled by a series of ubiquitous and specialized factors whose activities can be modulated by a variety of signaling events. Here we demonstrate that activity of the TGF-β1 promoter is increased by C/EBPβ, a DNA-binding transcription factor whose activity can be influenced by several immunomodulators, in astrocytes and microglial cells. Interestingly, expression of Smad3 and Smad4, the downstream regulators of the TGF-β1-signaling pathway, impairs the activity of C/EBPβ on the TGF-β1 promoter. Further, we demonstrate that MH2, a common domain among Smads that has protein-binding activities, interacts with C/EBPβ and decreases its association with a region of the TGF-β1 promoter that is responsive to C/EBPβ activation. Interestingly, the p65 subunit of nuclear factor-κB (NF-κB), which also interacts with C/EBPβ, cooperates with MH2 and decreased DNA-binding and transcriptional activities of C/EBPβ on the TGF-β1 promoter. These observations indicate that an autoregulatory mechanism, involving the MH2 domain of Smads, modulates activation of the TGF-β1 promoter by C/EBPβ. Further, our results show that the interplay between NF-κB and C/EBPβ has an impact on the ability of C/EBPβ to stimulate TGF-β1 transcription, hence, suggesting that the cross-communication of signaling pathways that modulate NF-κB and C/EBPβ may dictate the level of TGF-β1 promoter activity.
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Details
- Title
- Evidence for Activation of the TGF-[beta]1 Promoter by C/EBP[beta] and Its Modulation by Smads
- Creators
- Selvajothi Abraham - Temple UniversityThersa Sweet - Temple UniversityKamel Khalili - Temple UniversityBassel Sawaya - Temple UniversityShohreh Amini - Temple University
- Publication Details
- Journal of interferon & cytokine research, v 29(1)
- Publisher
- Mary Ann Liebert, Inc
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Epidemiology and Biostatistics
- Web of Science ID
- WOS:000262286900001
- Scopus ID
- 2-s2.0-58149343603
- Other Identifier
- 991021448056704721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology
- Immunology