Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation.

Verma, Inder M.; Stevenson, Jennifer K.; Schwarz, Edward M.; Antwerp, Daniel Van; Miyamoto, Shigeki

doi:10.1101/gad.9.22.2723

Cited by 1,648 publications

(1,359 citation statements)

References 109 publications

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“…NF-kB is a homo-or heterodimer protein belonging to the NF-kB/Rel family and may consist of five subunits as identified in mammalian cells: RelA or P65, RelB, c-rel, p50, and p52. The p50/p65 complex is the most prominent and is considered to be the prototype of the NF-kB factors (Verma et al 1995;Lilienbaum and Israël 2003). At equilibrium, the inactive form of NF-kB is located in the cytoplasm and is bound to inhibitory IkB molecules.…”

Section: Calcineurin and Nf-kb P65 In Type II Neuronsmentioning

confidence: 99%

Ouabain Induces Apoptotic Cell Death in Type I Spiral Ganglion Neurons, but not Type II Neurons

Lang

Schulte

Schmiedt

2005

JARO

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Application of ouabain to the intact round-window (RW) membrane of the gerbil cochlea induces apoptosis in most spiral ganglion neurons (SGNs), leaving a few neurons intact (Schmiedt et al. 2002). Here, physiological measures and immunostaining were used to examine the process of SGN degeneration at 3, 6, 12, and 24 h, 4 days, and 1 and 5 months after ouabain treatment. The few remaining neurons surviving up to 5 months after ouabain treatment were immunoreactive for peripherin, a type II neuron marker. Peripherin-positive cell counts indicate that about 7% of the SGNs in the gerbil cochlea are type II neurons, and these neurons survive intact after ouabain treatment. Ouabain exposure had little effect on the outer hair cell and lateral wall systems, even after a 5 month loss of auditory-nerve function. The cellular locations of cytochrome c, poly (ADP-ribose) polymerase (PARP), and activated caspase 3 were examined in control and ouabain-treated cochleas. A redistribution of cytochrome c in peripherinnegative (type I) neurons was observed at 3 h after ouabain exposure. Degraded PARP and activated caspase 3 were also detected in peripherin-negative SGNs at 6 and 24 h after treatment, respectively. These results suggest that the redistribution of cytochrome c is an early event during apoptosis in type I SGNs and that activation of PARP and caspase 3 are associated with apoptosis in these cells. Calcineurin and NF-kB are two important signaling pathways that may modulate cell survival in the central nervous system. Here, we found that calcineurin and NF-kB selectively labeled type II neurons. It is speculated that the high levels of calcineurin and NF-kB in type II SGNs, as compared with type I SGNs, may play protective roles in enhancing the survival of type II neurons exposed to ouabain.

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Section: Calcineurin and Nf-kb P65 In Type II Neuronsmentioning

confidence: 99%

Ouabain Induces Apoptotic Cell Death in Type I Spiral Ganglion Neurons, but not Type II Neurons

Lang

Schulte

Schmiedt

2005

JARO

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“…The NF-kB/Rel family of transcription factors regulates the expression of a variety of genes, including many involved in the regulation of immune and in¯ammatory responses, cellular proliferation, di erentiation, and inhibition of apoptosis (reviewed in Ghosh et al, 1998;Siebenlist et al, 1994;Verma et al, 1995). The proteins that comprise the NF-kB/Rel family have a region of homology of approximately 300 amino acids at their amino-termini, called the Rel Homology Domain (RHD), which confers DNA-binding properties, dimerization with other NF-kB proteins, and nuclear localization.…”

Section: Introductionmentioning

confidence: 99%

“…The functions of the NF-kB/Rel dimers are regulated by the inhibitory IkB proteins (reviewed in May and Ghosh, 1997;Verma et al, 1995). In the classic model of NF-kB activation, stimulation of cells by extracellular signals, such as tumor necrosis factor-a (TNF-a), results in activation of a kinase cascade leading to phosphorylation of speci®c regulatory serines near the amino terminus of the IkBa or IkBb by the IkB kinases (reviewed in May and Zandi and Karin, 1999).…”

Section: Introductionmentioning

confidence: 99%

Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes

Kim

Thakur

et al. 2000

Oncogene

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“…The NF-kB/Rel family of transcription factors play a key regulatory role in the expression of a variety of genes involved in several biological processes such as immune or in¯ammatory responses, growth, differentiation, and development (Baldwin, 1996;Verma et al, 1995). Members of this family are characterized by the presence of a highly conserved domain of 300 amino acids at the N-terminal region called the Rel homology domain (RHD) and consisting of a DNA-binding motif, a dimerization domain, and a nuclear localization signal.…”

Section: Introductionmentioning

confidence: 99%

“…Members of the NF-kB transcription factor family have been identi®ed in various organisms, ranging from¯ies to mammals (Baldwin, 1996;Verma et al, 1995). In mammals, other members of this family include p52 (NF-kB2), rel B, and the proto-oncogene c-Rel.…”

Section: Introductionmentioning

confidence: 99%

Activation of the wt1 Wilms' tumor suppressor gene by NF-κB

1998

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The Wilm's tumor suppressor gene, wt1, is expressed in a very de®ned spatial-temporal fashion and plays a key role in development of the urogenital system. Transacting factors governing wt1 expression are poorly de®ned. The presence of putative kB binding sites within the wt1 gene prompted us to investigate whether members of the NF-kB/Rel family of transcription factors are involved in regulating wt1 expression. In transient transfection assays, ectopic expression of p50 and p65 subunits of NF-kB stimulated wt1 promoter activity 10 ± 30-fold. Deletion mutagenesis revealed that NF-kB responsiveness is mediated by a short DNA fragment located within promoter proximal sequences of the major transcription start site. Two kB-binding sites are present in this region and form speci®c complexes with puri®ed NF-kB proteins, as revealed by electrophoretic mobility gel shift assays. Ectopic expression of p50 and p65 resulted in increased transcription of the endogenous wt1 gene, as revealed by nuclear run-on experiments. Taken together, these results indicate that members of the NF-kB/Rel family are important for activating expression of wt1 and reside upstream of the regulatory cascade leading to wt1 activation.

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Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation.

Cited by 1,648 publications

References 109 publications

Ouabain Induces Apoptotic Cell Death in Type I Spiral Ganglion Neurons, but not Type II Neurons

Ouabain Induces Apoptotic Cell Death in Type I Spiral Ganglion Neurons, but not Type II Neurons

Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes

Activation of the wt1 Wilms' tumor suppressor gene by NF-κB

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