Cloning of the DNA-binding subunit of human nuclear factor kappa B: the level of its mRNA is strongly regulated by phorbol ester or tumor necrosis factor alpha.

Meyer, Rolf; Hatada, Eunice N.; Hohmann, Hans‐Peter; Haiker, Monika; Bartsch, Cornelia; Röthlisberger, U; Lahm, Hans‐Werner; Schlaeger, Ernst‐Jürgen; Loon, Aaron P. van; Scheidereit, Claus

doi:10.1073/pnas.88.3.966

Cited by 211 publications

(150 citation statements)

References 28 publications

(32 reference statements)

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“…NFkB complexes are normally sequestered in the cytoplasm as precursors or by binding IkB (Beg et al, 1992;Finco and Baldwin, 1995), an association that is known to be disrupted by PKC/Ca 2+ mediated phosphorylation and proteolysis of IkB and p105 (the p50 precursor) (Israel, 1995;Li et al, 1995;Verma et al, 1995). Phosphorylation of p50 also results in a higher level of DNA binding stability (Li et al, 1994), and increased p105 transcription is mediated by PMA (Meyer et al, 1991;Cogswell et al, 1993). All of these mechanisms are potentially involved in the induction of NFkB binding observed.…”

Section: Discussionmentioning

confidence: 99%

ETS1, NFκB and AP1 synergistically transactivate the human GM – CSF promoter

et al. 1997

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Activation of helper T cells results in coordinate expression of a number of cytokines involved in di erentiation, proliferation and activation of the haematopoietic system. Granulocyte-macrophage colony stimulating factor (GM ± CSF) is one such cytokine, whose increased expression results mostly from increases in transcription. Cis-acting elements with NFkB, AP1 and ETS-like binding motifs have been identi®ed in the promoter region of the GM ± CSF gene, and are important or essential for transcriptional activity following T cell activation. ETS1 is a transcription factor of the ETS family that is expressed in T cells. We have previously shown that ETS1 can transactivate GM ± CSF in Jurkat T cells, but only after the cells have been stimulated by treatment with PMA and ionomycin, agents that mimic T cell activation. Thus we proposed that ETS1, which is expressed constitutively in Jurkat cells, may act in concert with PMA/ionomycin inducible factors. Here we show that ETS1 can transactivate a GM ± CSF reporter construct in unstimulated Jurkat cells, providing that either NFkB or AP1 transcription factors are supplied by co-transfection. We con®rm that binding of endogenous NFkB and AP1 is induced following PMA/ionomycin treatment of T cells. Transactivation by ETS1, NFkB and AP1 is synergistic, and mutation of the individual binding sites reveals that the transcriptional activities of these factors are interdependent. Our results suggest that constitutive ETS1, and inducible NFkB and AP1, cooperate as part of a higher order transcriptional complex in activated T cells.

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Section: Discussionmentioning

confidence: 99%

ETS1, NFκB and AP1 synergistically transactivate the human GM – CSF promoter

et al. 1997

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“…IkBa degradation allows NF-kB to translocate from its inactive cytoplasmic location into the nucleus and initiate the transcriptional activation of targeted genes. 27 Recently, it has been shown that oridonin treatment is associated with blockage of NF-kB signal pathways. 25,28 Directly interfering with the DNA-binding activity of NF-kB to its response DNA sequence, oridonin has an additional impact on NF-kB nuclear translocation by affecting IkBa phosphorylation and degradation.…”

Section: Discussionmentioning

confidence: 99%

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-κB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner

et al. 2006

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Diterpenoids isolated from Labiatae family herbs have strong antitumor activities with low toxicity. In this study, Eriocalyxin B (EriB), a diterpenoid extracted from Isodon eriocalyx, was tested on human leukemia/lymphoma cells and murine leukemia models. Acute myeloid leukemia cell line Kasumi-1 was most sensitive to EriB. Significant apoptosis was observed, concomitant with Bcl-2/Bcl-X L downregulation, mitochondrial instability and caspase-3 activation. AML1-ETO oncoprotein was degraded in parallel to caspase-3 activation. EriB-mediated apoptosis was associated with NF-jB inactivation by preventing NF-jB nuclear translocation and inducing IjBa cleavage, and disturbance of MAPK pathway by downregulating ERK1/2 phosphorylation and activating AP-1. Without affecting normal hematopoietic progenitor cells proliferation, EriB was effective on primary t(8;21) leukemia blasts and caused AML1-ETO degradation. In murine t(8;21) leukemia models, EriB remarkably prolonged the survival time or decreased the xenograft tumor size. Together, EriB might be a potential treatment for t(8;21) leukemia by targeting AML1-ETO oncoprotein and activating apoptosis pathways.

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“…3,26,27 To study the effects on p100 mRNA expression, monocytes were stimulated with TNF-␣ (500 U/ml) and IL-1␤ (100 U/ml) at different points of time. The results presented in Figures 5a and 6a show a time-dependent increase of p100 mRNA expression with optimal expression at 1 h and 3 h of stimulation respectively.…”

Section: Signalling Pathways Involved In the P100 Regulationmentioning

confidence: 99%

Regulation of p100 (NFKB2) expression in human monocytes in response to inflammatory mediators and lymphokines

Wit¹,

Dokter²,

Koopmans³

et al. 1998

Leukemia

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The transcription factor NF-B plays an important role in the regulated expression of cytokines in human monocytes. A p100 subunit of NF-B has IB-like properties by sequestering the p65 transactivating subunit in the cytosol of cells. In transient transfection assays we demonstrated that p100 has an inhibitory effect on the NF-B-dependent IL-6 promoter activity. In view of this finding, we studied the regulation of the p100 subunit in human monocytes in response to LPS, the inflammatory cytokines IL-1␤ and TNF-␣ and lymphokines. The results demonstrate that LPS, IL-1␤, and TNF-␣ induce p100 expression at mRNA and protein level while IFN-␥, IL-3 and IL-4/IL-10 have no effect. The induction of p100 expression was shown to be mediated by a two-fold increase in the p100 transcription rate and a two-fold increase in p100 mRNA stability. Furthermore the p100 mediated upregulation was dependent on a tyrosine kinase dependent pathway rather than the protein kinase C pathway. NF-B is a complex of either p50 homodimers or a p50/p65 heterodimer. The latter is known to strongly autoregulate p100 transcription. We therefore examined the composition of NF-B induced by LPS vs the different lymphokines. LPSinduced NF-B showed a distinct p65 supershift whereas the composition of NF-B induced by different lymphokines did not show a change in p65. We conclude that the p100 subunit of the transcription factor NF-B is induced by different inflammatory mediators while lymphokines fail to induce p100 expression which may be caused by the induction of NF-B predominantly consisting of p50 homodimers.

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Cloning of the DNA-binding subunit of human nuclear factor kappa B: the level of its mRNA is strongly regulated by phorbol ester or tumor necrosis factor alpha.

Cited by 211 publications

References 28 publications

ETS1, NFκB and AP1 synergistically transactivate the human GM – CSF promoter

ETS1, NFκB and AP1 synergistically transactivate the human GM – CSF promoter

Eriocalyxin B induces apoptosis of t(8;21) leukemia cells through NF-κB and MAPK signaling pathways and triggers degradation of AML1-ETO oncoprotein in a caspase-3-dependent manner

Regulation of p100 (NFKB2) expression in human monocytes in response to inflammatory mediators and lymphokines

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