An AP1 binding site upstream of the kappa immunoglobulin intron enhancer binds inducible factors and contributes to expression

Schanke, Judith T.; Marcuzzi, Adriana; Podzorski, R P; Ness, Brian Van

doi:10.1093/nar/22.24.5425

Cited by 21 publications

(17 citation statements)

References 26 publications

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“…To explore the potential role of Net-b in B-cell development, we studied the pre-B cell line, 70Z/3, which can be induced to differentiate with LPS. LPS is known to stimulate SRE activity (24), Fos-Jun DNA binding activity (43), and p38 MAP kinase (16,17). We found that LPS induction of 70Z/3 pre-B-cell differentiation increases TC-forming activity to a small extent.…”

Section: Discussionmentioning

confidence: 99%

Net-b, a Ras-Insensitive Factor That Forms Ternary Complexes with Serum Response Factor on the Serum Response Element of the fos Promoter

Giovane

Sobieszczuk

Ayadi

et al. 1997

Molecular and Cellular Biology

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The Ras signalling pathway targets transcription factors such as the ternary complex factors that are recruited by the serum response factor to form complexes on the serum response element (SRE) of the fos promoter. We have identified a new ternary complex factor, Net-b. We report the features of the net gene and show that it produces several splice variants, net-b and net-c. net-b RNA and protein are expressed in a variety of tissues and cell lines. net-c RNA is expressed at low levels, and the protein was not detected, raising the possibility that it is a cryptic splice variant. We have studied the composition of ternary complexes that form on the SRE of the fos promoter with extracts from fibroblasts (NIH 3T3) cultured under various conditions and pre-B cells (70Z/3) before and after differentiation with lipopolysaccharide (LPS). The fibroblast complexes contain mainly Net-b followed by Sap1 and Elk1. Net-b complexes, as well as Sap1 and Elk1, are induced by epidermal growth factor (EGF) stimulation of cells cultured in low serum. Pre-B-cell complexes contain mainly Sap1, with less of Net-b and little of Elk1. There is little change upon LPS-induced differentiation compared to the increase with EGF in fibroblasts. We have also found that Net-b is a nuclear protein that constitutively represses transcription. Net-b is not activated by Ras signalling, in contrast to Net, Sap1a, and Elk1. We have previously reported that down-regulation of Net proteins with antisense RNA increases SRE activity. The increase in SRE activity is observed at low serum levels and is even greater after serum stimulation, showing that the SRE is under negative regulation by Net proteins and the level of repression increases during induction. Net-b, the predominant factor in ternary complexes in fibroblasts, may both keep the activity of the SRE low in the absence of strong inducing conditions and rapidly shut the activity off after stimulation.

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Section: Discussionmentioning

confidence: 99%

Net-b, a Ras-Insensitive Factor That Forms Ternary Complexes with Serum Response Factor on the Serum Response Element of the fos Promoter

Giovane

Sobieszczuk

Ayadi

et al. 1997

Molecular and Cellular Biology

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“…The human Igκ gene contains an NF-κB site and a perfect consensus AP-1 site within the iEκ and the downstream iEκ. In B lymphocytes, both enhancers can be activated by nuclear factor NF-κB and AP-1 at different degrees (41,42).…”

Section: Some Regulatory Mechanisms Of Ig Expressed In Cancer Cellsmentioning

confidence: 99%

Immunoglobulin Expression and Its Biological Significance in Cancer Cells

Zheng

Liu

et al. 2008

Cell Mol Immunol

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“…7], immunoglobulins (e.g., light chain; ref. 8), inflammatory enzymes (e.g., COX-2; ref. 9), and matrix metalloproteinases (e.g., MMP-13; ref.…”

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confidence: 99%

SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase

Bennett¹,

Sasaki²,

Murray³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

2,358

1,772

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Jun N-terminal kinase (JNK) is a stress-activated protein kinase that can be induced by inflammatory cytokines, bacterial endotoxin, osmotic shock, UV radiation, and hypoxia. We report the identification of an anthrapyrazolone series with significant inhibition of JNK1, -2, and -3 (K i ‫؍‬ 0.19 M). SP600125 is a reversible ATPcompetitive inhibitor with >20-fold selectivity vs. a range of kinases and enzymes tested. In cells, SP600125 dose dependently inhibited the phosphorylation of c-Jun, the expression of inflammatory genes COX-2, IL-2, IFN-␥, TNF-␣, and prevented the activation and differentiation of primary human CD4 cell cultures. In animal studies, SP600125 blocked (bacterial) lipopolysaccharideinduced expression of tumor necrosis factor-␣ and inhibited anti-CD3-induced apoptosis of CD4 ؉ CD8 ؉ thymocytes. Our study supports targeting JNK as an important strategy in inflammatory disease, apoptotic cell death, and cancer.

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An AP1 binding site upstream of the kappa immunoglobulin intron enhancer binds inducible factors and contributes to expression

Cited by 21 publications

References 26 publications

Net-b, a Ras-Insensitive Factor That Forms Ternary Complexes with Serum Response Factor on the Serum Response Element of the fos Promoter

Net-b, a Ras-Insensitive Factor That Forms Ternary Complexes with Serum Response Factor on the Serum Response Element of the fos Promoter

Immunoglobulin Expression and Its Biological Significance in Cancer Cells

SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase

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