The Mammalian Transcriptional Repressor RBP (CBF1) Regulates Interleukin-6 Gene Expression

Kannabiran, Chitra; Zeng, Xiaoya; Vales, L D

doi:10.1128/mcb.17.1.1

Cited by 69 publications

(65 citation statements)

References 42 publications

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“…The promoter of the adenovirus pIX polypeptide contains a consensus binding site for CBF1/RBP-J that mediates repression both in vitro and in vivo (Dou et al 1994). A similar repressive function has been ascribed to CBF1/RPB-J binding sites in the IL-6 and NF-B2 promoters (Kannabiran et al 1997;Plaisance et al 1997;Miyazawa et al 1998). Direct evidence for CBF1/RPB-J 's repressive activity comes from the finding that a GAL4-CBF1 fusion protein can repress activity of a thymidine kinase (TK) promoter linked to GAL4-binding sites (Hsieh and Hayward 1995).…”

mentioning

confidence: 90%

A histone deacetylase corepressor complex regulates the Notch signal transduction pathway

Kao¹,

Ordentlich²,

et al. 1998

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mentioning

confidence: 90%

A histone deacetylase corepressor complex regulates the Notch signal transduction pathway

Kao¹,

Ordentlich²,

et al. 1998

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“…IL-6 pCAT promoter constructs were originally obtained from Dr. L. Vales (UMDNJ) (23,45). IL-6 promoter regions were subcloned into pGL-3 Basic (Promega, Madison, WI, USA), a reporter vector containing the firefly luciferase gene.…”

Section: Transient Transfection and Reporter Gene Assaysmentioning

confidence: 99%

p38 MAPK Regulates IL‐1β Induced IL‐6 Expression Through mRNA Stability in Osteoblasts

Patil

Zhu

Rossa

et al. 2004

Immunological Investigations

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Osteoblast-derived IL-6 functions in coupled bone turnover by supporting osteoclastogenesis favoring bone resorption instead of bone deposition. Gene regulation of IL-6 is complex occurring both at transcription and post-transcription levels. The focus of this paper is at the level of mRNA stability, which is important in IL-6 gene regulation. Using the MC3T3-E1 as an osteoblastic model, IL-6 secretion was dose dependently decreased by SB203580, a p38 MAPK inhibitor. Steady state IL-6 mRNA was decreased with SB203580 (2μM) ca. 85% when stimulated by IL-1β (1 5ng/ml). These effects require de novo protein synthesis as they were inhibited by cycloheximide. p38 MAPK had minor effects on proximal IL-6 promoter activity in reporter gene assays. A more significant effect on IL-6 mRNA stability was observed in the presence of SB203580. Western blot analysis confirmed that SB203580 inhibited p38 MAP kinase, in response to IL-1β in a dose dependent manner in MC3T3-E1 cells. Stably transfected MC3T3-E1 reporter cell lines (MC6) containing green fluorescent protein (GFP) with the 3′ untranslated region of IL-6 was constructed. Results indicated that IL-1β, TNFα, LPS but not parathyroid hormone (PTH) could increase GFP expression of these reporter cell lines. Endogenous IL-6 and reporter gene eGFP-IL-6 3′ UTR mRNA was regulated by p38 in MC6 cells. In addition, transient transfection of IL-6 3′ UTR reporter cells with immediate upstream MAP kinase kinase-3 and -6 increased GFP expression compared to mock transfected controls. These results indicate that p38 MAPK regulates IL-1β-stimulated IL-6 at a post transcriptional mechanism and one of the primary targets of IL-6 gene regulation is the 3′ UTR of IL-6.

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“…Our alternate hypothesis was that the complex might contain RBP-J because it has been shown that RBP-J binds to certain B sites (30,32). On some gene promoters, RBP-J competes with NF-B proteins to repress NF-B-induced transcription (37,38,43). Interestingly, we found that the complex present in band D contained both C/EBP and RBP-J .…”

Section: Discussionmentioning

confidence: 54%

“…Other mechanisms for the role of RBP-J in gene expression have been described. For example, adjacent C/EBP-binding and RBP-J binding sites are present on the IL-6 promoter and it has been shown that RBP-J suppresses activation of the IL-6 promoter by NF-B and C/EBP␤ (43,49).…”

Section: Discussionmentioning

confidence: 99%

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A Novel RBP-Jκ-Dependent Switch from C/EBPβ to C/EBPζ at the C/EBP Binding Site on the C-Reactive Protein Promoter

Singh

Voleti

Agrawal

2007

The Journal of Immunology

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Regulation of basal and cytokine (IL-6 and IL-1β)-induced expression of C-reactive protein (CRP) in human hepatoma Hep3B cells occurs during transcription. A critical transcriptional regulatory element on the CRP promoter is a C/EBP binding site overlapping a NF-κB p50 binding site. In response to IL-6, C/EBPβ and p50 occupy the C/EBP-p50 site on the CRP promoter. The aim of this study was to identify the transcription factors occupying the C/EBP-p50 site in the absence of C/EBPβ. Accordingly, we treated Hep3B nuclear extract with a C/EBP-binding consensus oligonucleotide to generate an extract lacking active C/EBPβ. Such treated nuclei contain only C/EBPζ (also known as CHOP10 and GADD153) because the C/EBP-binding consensus oligonucleotide binds to all C/EBP family proteins except C/EBPζ. EMSA using this extract revealed formation of a C/EBPζ-containing complex at the C/EBP-p50 site on the CRP promoter. This complex also contained RBP-Jκ, a transcription factor known to interact with κB sites. RBP-Jκ was required for the formation of C/EBPζ-containing complex. The RBP-Jκ-dependent C/EBPζ-containing complexes were formed at the C/EBP-p50 site on the CRP promoter in the nuclei of primary human hepatocytes also. In luciferase transactivation assays, overexpressed C/EBPζ abolished both C/EBPβ-induced and (IL-6 + IL-1β)-induced CRP promoter-driven luciferase expression. These results indicate that under basal conditions, C/EBPζ occupies the C/EBP site, an action that requires RBP-Jκ. Under induced conditions, C/EBPζ is replaced by C/EBPβ and p50. We conclude that the switch between C/EBPβ and C/EBPζ participates in regulating CRP transcription. This process uses a novel phenomenon, that is, the incorporation of RBP-Jκ into C/EBPζ complexes solely to support the binding of C/EBPζ to the C/EBP site.

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The Mammalian Transcriptional Repressor RBP (CBF1) Regulates Interleukin-6 Gene Expression

Cited by 69 publications

References 42 publications

A histone deacetylase corepressor complex regulates the Notch signal transduction pathway

A histone deacetylase corepressor complex regulates the Notch signal transduction pathway

p38 MAPK Regulates IL‐1β Induced IL‐6 Expression Through mRNA Stability in Osteoblasts

A Novel RBP-Jκ-Dependent Switch from C/EBPβ to C/EBPζ at the C/EBP Binding Site on the C-Reactive Protein Promoter

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