NF-κB Subunit Regulation in Nontransformed CD4
            <sup>+</sup>
            T Lymphocytes

Kang, ⋅Sang-Mo; Tran, Andy; Grilli, Mariagrazia; Lenardo, Michael J.

doi:10.1126/science.1604322

Cited by 314 publications

(239 citation statements)

References 51 publications

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“…In some experimental systems p50/p50 homodimers activated transcription from promoters with speci®c kB sites (Collart et al, 1990;Fujita et al, 1992Fujita et al, , 1993Kretzschmar et al, 1992;Schouten et al, 1995;Ten et al, 1992). In other experimental systems these homodimers were unable to activate gene transcription (Beg et al, 1992;Franzoso et al, 1992;Kang et al, 1992;Plaksin et al, 1993;Schmitz and Baeuerle, 1991). It seems that p50/p50 displays high a nity binding for many distinct kB motifs but provides a strong transcriptional activation only when adopting a speci®c conformation induced by certain kB motifs but not others (Fujita et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Pérez²,

et al. 1999

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To elucidate the possible role of NF-kB in mouse skin carcinogenesis we studied the expression of p50 (NFkB1), p52 (NF-kB2), p65 (RelA) and IkB-a inhibitor as well as kB-binding activity in adult SENCAR mouse skin, skin papillomas, and squamous cell carcinomas (SCC) generated by a two-stage carcinogenesis protocol. We found that in normal epidermis all of the above proteins were mostly expressed in the cytoplasm of basal cells. Western blot analysis revealed a dramatic increase of p50 and p52 expression in mouse skin tumors starting from the middle stage of promotion. We also found that the level of IkB-a protein in many late papillomas and SCC was lower than in normal epidermis. Results of EMSA showed an increase in kB-binding activity in mouse skin tumors and suggested that p50 is the major component of constitutive kB-binding complexes in normal epidermis and in tumors. It has been shown that nuclear IkB protein Bcl-3 is able to increase p50/p50 homodimer binding to the di erent kB sites in mouse thymocytes. Our ®nding on Bcl-3 overexpression in late papillomas and SCC could explain the selective increase of p50-related kB-binding in mouse skin tumors. Thus, our results strongly suggest the important role of p50 in skin carcinogenesis.

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Section: Discussionmentioning

confidence: 99%

Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Pérez²,

et al. 1999

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“…In this context, it is particularly interesting that LPS-activated cells expressed a higher level of p50 homodimers relative to heterodimers compared to that of anti-CD40-activated cells. It has been shown that excess of p50 homodimers can reduce activity on some promoters, presumably by replacing binding of p65 or c-Rel-containing heterodimers, which have higher transactivating potential [57,58]. On the other hand, it is possible that the difference in the level of GL ␥1 transcripts induced by LPS and anti-CD40 is independent of NF-B.…”

Section: Discussionmentioning

confidence: 99%

Characterization of CD40‐Dependent Immunoglobulin Class Switching

et al. 1999

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Ström L, Laurencikiené J, Miskiniené A, Severinson E. Characterization of CD40-Dependent Immunoglobulin Class Switching. Scand J Immunol 1999;49;523-532 Previous studies have shown that signalling via CD40 together with cytokines stimulates immunoglobulin (Ig) class switching in B cells. This process includes induction of germline (GL) transcripts and switch recombination. Using an agonistic rat anti-mouse CD40 monoclonal antibody (MoAb), we investigated the role of CD40 signalling in these molecular events. We found that stimulation of murine B cells induced high steady-state levels of germline ␥1, ␥2b and low levels of ⑀ transcripts. No detectable ␥2a or ␣RNA were found and the level of ␥3 transcripts was high both in stimulated and unstimulated cells. Although cells treated with anti-CD40 MoAb had high levels of GL ␥1 and ␥3 transcripts, we failed to detect switching to IgG1 or IgG3. However, anti-CD40 MoAb-stimulated cells increased expression of IgG2b. Interestingly, anti-CD40 plus interleukin (IL)-5 induced switching to IgG1. Previous work has demonstrated that CD40 signalling, but not lipopolysaccharide (LPS), induces the ␥1 promoter and that NF-B motifs are important. We show here that both LPS and anti-CD40 activated NF-B proteins binding to the ␥1 promoter. The bound NF-B complexes were different with regard to total concentration and subunit composition. In the light of our data, the mechanism of CD40-mediated Ig class switching is discussed.

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“…Polyclonal rabbit antip50 antibodies were prepared against bacterially produced and affinity purified recombinant mouse p50 as described in Ref. 29, anti-p65 and anti-c-Rel antibodies were from Santa Cruz Biotechnologies.…”

Section: Methodsmentioning

confidence: 99%

Interleukin-1β and Glutamate Activate the NF-κB/Rel Binding Site from the Regulatory Region of the Amyloid Precursor Protein Gene in Primary Neuronal Cultures

Grilli

Goffi

Memo

et al. 1996

Journal of Biological Chemistry

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143

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We originally reported that members of the family of transcription factors NF-B/Rel can specifically recognize two identical sequences, referred to as APP B sites, which are present in the 5 -regulatory region of the APP gene. Here we show that the APP B sites interact specifically with a complex which contains one of the subunits of the family, defined as p50 protein, and that they act as positive modulators of gene transcription in cells of neural origin. Additionally, the nuclear complex specifically binding to the APP B sites is constitutively expressed in primary neurons from rat cerebellum and it is up-regulated in response to both the inflammatory cytokine interleukin-1␤ (IL-1␤) and the excitatory amino acid glutamate. Since IL-1, whose levels are known to be induced in brain of individuals affected by Alzheimer's disease, and glutamate, are stimuli which have been regarded as major actors on the stage of neurodegenerative processes, we believe our evidence as potentially relevant for understanding the neuropathology associated with Alzheimer's disease.Alzheimer's disease (AD) 1 is a neurodegenerative disorder characterized by abnormal deposition of extracellular congophilic plaques in the brain. The main constituent of plaques is a 39-to 43-amino acid peptide, named ␤-amyloid, which is a proteolytic fragment of the amyloid precursor protein (APP) (1). In recent years, most experimental studies have been aimed at understanding the mechanisms of ␤-amyloid formation and deposition and at identifying potential risk factors which may favor these processes. In particular, APP gene mutations occurring in families with Familial AD have been correlated with disturbance in protein processing, which in turn, may predispose to ␤ amyloid formation (2, 3). However, since APP gene mutations represent a minor percentage of AD cases, it is evident that other mechanisms may exist to account for ␤-amyloid deposition. In this regard, it should not be underestimated that overexpression of the APP gene may be involved in the pathogenetic mechanisms of amyloid formation, at least in some clinical forms of the disease. Several observations underscore the potential contribution of the APP gene overexpression to favoring AD neuropathology: (i) the marked accumulation of ␤-amyloid which correlates with increased levels of APP mRNA in trisomy 21 (Down's syndrome) (4); (ii) the increased levels of APP gene transcripts in specific areas of the AD brains (5-7); (iii) the increased APP mRNA transcription in cultured fibroblasts from the Familial Alzheimer's disease-1 family (8). In addition, post-mitotic neurons which overexpress full-length APP were shown to degenerate and accumulate large amounts of amyloidogenic C-terminal fragments (9). The promoter region of the APP gene (10) has been shown to contain binding sequences for several known transcription factors (11)(12)(13)(14)(15)(16)(17)(18)(19). We reported recently (20) that a novel regulatory pathway for APP gene control at the transcriptional level may involve members of the NF...

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NF-κB Subunit Regulation in Nontransformed CD4 ⁺ T Lymphocytes

Cited by 314 publications

References 51 publications

Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Characterization of CD40‐Dependent Immunoglobulin Class Switching

Interleukin-1β and Glutamate Activate the NF-κB/Rel Binding Site from the Regulatory Region of the Amyloid Precursor Protein Gene in Primary Neuronal Cultures

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NF-κB Subunit Regulation in Nontransformed CD4 + T Lymphocytes

Cited by 314 publications

References 51 publications

Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Increased expression of p50-NF-κB and constitutive activation of NF-κB transcription factors during mouse skin carcinogenesis

Characterization of CD40‐Dependent Immunoglobulin Class Switching

Interleukin-1β and Glutamate Activate the NF-κB/Rel Binding Site from the Regulatory Region of the Amyloid Precursor Protein Gene in Primary Neuronal Cultures

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NF-κB Subunit Regulation in Nontransformed CD4 ⁺ T Lymphocytes