Interaction of the nuclear protein CBF1 with the  B site of the IL-6 gene promoter

Palmieri, Marta; Sasso, Maurizio; Monese, Rossana; Merola, Marcello; Faggioli, L; Tovey, Michaël G.; Furia, Adriana

doi:10.1093/nar/27.13.2785

Cited by 32 publications

(23 citation statements)

References 38 publications

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“…The NF-B site of the IL-6 promoter overlaps with a binding site for CBF1 which can repress NF-B-dependent transcription driven by p50:p65 heterodimers (37,38). We found that anti-CD40 treatment of FSDC generated a prolonged elevation of CBF1 DNA binding while induction of p50:p65 binding was transient.…”

Section: Discussionmentioning

confidence: 74%

See 1 more Smart Citation

CD40 Induces Interleukin-6 Gene Transcription in Dendritic Cells

Mann¹,

Oakley²,

Johnson³

et al. 2002

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 74%

“…DNA-binding site in the IL-6 promoter overlaps with a sequence that acts as a binding site for the transcriptional repressor CBF1 (also designated RBP-J) (37,38). Since this overlapping sequence was included in our NF-B EMSA probe, we therefore investigated the possibility that NF-B complex 1 may be due to binding of CBF1.…”

Section: Figmentioning

confidence: 99%

CD40 Induces Interleukin-6 Gene Transcription in Dendritic Cells

Mann¹,

Oakley²,

Johnson³

et al. 2002

Journal of Biological Chemistry

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“…M (not shown). CBF-1, a member of the Notch family binding a sequence in the NF-‹ B site of IL-6 promoter [24], remained substantially unmodified, thus ensuring equal protein probing and treatment specificity.…”

Section: P38 Regulates the Basal Activation Of Both Nf-k B And Nf-il6mentioning

confidence: 99%

“…P]ATP-labeled double-stranded probe encompassing the NF-‹ B binding site of the IL-6 promoter [24]. Cell extracts (6 ?…”

mentioning

confidence: 99%

p38 MAPK is a critical regulator of the constitutive and the β4 integrin‐regulated expression of IL‐6 in human normal thymic epithelial cells

et al. 2003

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Cytokines and adhesion receptors are key mediators in the dialog occurring between thymic epithelial cells (TEC) and thymocytes and regulating T cell maturation and epithelial embryonic differentiation. Among cytokines, IL-6 can be critical in the thymus, fostering proliferation, differentiation and/or survival of both TEC and thymocytes. We have previously reported in human normal TEC that clustering of the laminin receptor § 6 g 4 integrin induced by thymocyte contact or monoclonal antibody-mediated cross-linking regulates IL-6 gene expression via activation of NF-‹ B and NF-IL6 transactivators. Here we show that § 6 g 4 integrin activates p38 mitogen-activated protein kinase (MAPK) and that p38 is essential for IL-6 gene expression. In fact, g 4 cross-linking activated p38 and extracellular signalregulated kinase (ERK) MAPK, Rac1, p21-activated protein kinase 1 (PAK1) and MAPK kinases (MKK) 3/MKK6. However, pharmacological blockade of p38 or ERK demonstrated that p38 inhibition abrogated both basal and g 4 integrin-induced production of IL-6 preventing NF-‹ B and NF-IL6 activation, whereas ERK inhibition reduced IL-6 production, hampering only NF-‹ B activation. Overall, our results indicate that p38 MAPK and § 6 g 4 integrin, expressed by TEC throughout their life, are critical regulators of the intrathymic availability of a cytokine controlling fate and functions of cells governing development and maintenance of thymic architecture and immune responses.

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“…In this study we provide evidence that HSC activation is associated with induced expression of the ubiquitously expressed transcriptional repressor RBP-J (hereafter termed CBF1), which is able to bind to a subset of NF-B sites that overlap with consensus CBF1-binding sites (37)(38)(39)(40). We have mapped an overlapping NF-B/CBF1-binding site (B2 site) in the human IB␣ promoter and have shown that overexpression of CBF1 resulted in a profound repression of IB␣ gene transcription and protein expression.…”

mentioning

confidence: 99%

Basal Expression of IκBα Is Controlled by the Mammalian Transcriptional Repressor RBP-J (CBF1) and Its Activator Notch1

Oakley

Mann

Ruddell

et al. 2003

Journal of Biological Chemistry

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By using the hepatic stellate cell (HSC) as a paradigm for cells that undergo long term re-programming of NF-B-dependent transcription, we have determined a novel mechanism by which mammalian cells establish their basal NF-B activity. Elevation of NF-B activity during HSC activation is accompanied by induction of CBF1 expression and DNA binding activity. We show that the transcriptional repressor CBF1 interacts with a dual NF-B/CBF1-binding site (B2) in the IB␣ promoter. Nucleotide substitutions that disrupt CBF1 binding to the B2 site result in an elevation of IB␣ promoter activity and loss of responsiveness of the promoter to a transfected CBF1 reporter vector. Overexpression of CBF1 in COS1 cells was associated with markedly reduced IB␣ protein expression and elevated NF-B DNA binding activity. CBF1-induced repression of IB␣ promoter activity was reversed in HSC transfected with the Notch1 intracellular domain (NICD). The ability of NICD to enhance IB␣ gene transcription was confirmed in COS1 cells and was found to be dependent on an intact RAM domain of NICD that has been shown previously to help mediate the interaction of NICD with CBF1. One of the mechanisms by which NICD is thought to convert CBF1 into an activator of transcription is via the recruitment of transcriptional co-activators/histone acetylases to gene promoters. Co-transfection of HSC with NICD and p53 caused a diminution of IB␣ promoter activity, by contrast overexpression of p300 enhanced IB␣ promoter function. Taken together, these data suggest that basal IB␣ expression (and as a consequence NF-B activity) is under the control of the various components of the CBF1/Notch signal transduction pathway.The transcription factor NF-B is a key regulator of the growth, differentiation, and fate of mammalian cells (1). In its active form NF-B is found in the nucleus as either a heterodimer or a homodimer composed of five different members of the Rel family of proteins (p65, p50, p52, c-Rel, and RelB) (1). Active NF-B can bind to its target DNA sequence (GGGRN-NYYCC) and activate the transcription of a vast number and wide range of genes (2). Given the importance of NF-B as a regulator of cell function, it is essential that its transcriptional activity is subject to exquisite control mechanisms. Most cells only express low levels of basal nuclear NF-B activity, with the majority of Rel dimers being sequestered in the cytoplasm in a complex with an inhibitory IB protein. The three most important IB proteins, IB␣, IB␤, and IB⑀, inhibit NF-B function by masking nuclear localization and DNA binding signals (1, 3). These inhibitors are pivotal regulators of NF-Bdependent gene expression as they can be degraded in response to a wide variety of epigenetic stimulators and in doing so release active NF-B which can then translocate to the nucleus and activate transcription (3). Perturbation of IB control of NF-B has been associated with many pathological conditions including chronic inflammatory diseases, persistence of viral infections, and cancer (4 -7). Ther...

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Interaction of the nuclear protein CBF1 with the B site of the IL-6 gene promoter

Cited by 32 publications

References 38 publications

CD40 Induces Interleukin-6 Gene Transcription in Dendritic Cells

CD40 Induces Interleukin-6 Gene Transcription in Dendritic Cells

p38 MAPK is a critical regulator of the constitutive and the β4 integrin‐regulated expression of IL‐6 in human normal thymic epithelial cells

Basal Expression of IκBα Is Controlled by the Mammalian Transcriptional Repressor RBP-J (CBF1) and Its Activator Notch1

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