Structure, Regulation and Function of NF-kappaB

Siebenlist, Ulrich; Franzoso, Guido; Brown, Keith

doi:10.1146/annurev.cb.10.110194.002201

Cited by 2,019 publications

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“…This review describes common stereochemical features of several crystallographic Rel/NF-kB:DNA complexes, and, in the context of these models, provides some insights into how phosphorylation, protein sequence variation, DNA sequence variation, and IkB modulation can a ect the DNA binding characteristics of NF-kB. Other more general reviews of NF-kB are also available (Baeuerle and Henkel, 1994;Baldwin, 1996;Siebenlist et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

Regulation of DNA binding by Rel/NF-κB transcription factors: structural views

1999

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Rel/NF-kB transcription factors form homo-and heterodimers with di erent DNA binding site speci®cities and DNA binding a nities. Several intracellular pathways evoked by a wide range of biological factors and environmental conditions can lead to the activation of Rel/NF-kB dimers by signaling degradation of the inhibitory IkB protein. In the nucleus Rel/NF-kB dimers modulate the expression of a variety of genes including those encoding cytokines, growth factors, acute phase response proteins, immunoreceptors, other transcription factors, cell adhesion molecules, viral proteins and regulators of apoptosis. The primary focus of this review is on structural and functional aspects of Rel/NFkB:DNA complexes and their formation. The salient features of the Rel/NF-kB dimer:DNA structure are described, as are modes of transcriptional regulation by phosphorylation, altered DNA binding properties, varying protein conformations, and interactions with IkB proteins.

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Section: Introductionmentioning

confidence: 99%

Regulation of DNA binding by Rel/NF-κB transcription factors: structural views

1999

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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%

Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes

Kim

Thakur

et al. 2000

Oncogene

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“…To this end, we used TNFa, a well-known inducer of NF-kB in many cell types (Siebenlist et al, 1994). For these experiments, nuclear extracts were prepared from serum-starved Caco-2-H, Caco-2-MT and Caco-2-T cells which had been treated for 1 h in the presence or absence of 10 ng/ml of TNFa.…”

Section: Resultsmentioning

confidence: 99%

“…This ubiquitous transcription factor, whose expression is altered in some cancer cells ( Van't Veer et al, 1993;Bours et al, 1994;Mukhopadhyay et al, 1995), is known to control the expression of numerous genes including genes coding for proteins that are important for cell adhesion (Voraberger et al, 1991;Whelan et al, 1991;Iademarco et al, 1992). NF-kB was originally described as being present in the cytosol of many cell types as an inactive heterodimer composed of 50 kDa (p50, NF-kB1) and 65-kDa (p65, Rel A) subunits and bound to IkB-a, one of the inhibitor proteins of the IkB family (Grilli et al, 1993;Grimm and Baeuerle, 1993;Siebenlist et al, 1994). Cloning of the cDNAs encoding NF-kB p50 and p65 subunits revealed that both proteins are homologous to the product of the c-rel proto-oncogene.…”

Section: Introductionmentioning

confidence: 99%

Down-regulation of NF-κB activity and NF-κB p65 subunit expression by ras and polyoma middle T oncogenes in human colonic Caco-2 cells

et al. 1997

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The products of ras and src proto-oncogenes are frequently activated in a constitutive state in human colorectal cancer. In this study we attempted to establish whether the tumorigenic progression induced by oncogenic activation of p21 ras or pp60 c-src in human colonic cells is associated with alterations of the activity and expression of nuclear factor kB (NF-kB), a transcription factor suspected to participate in the development of cancer. To this end, we used Caco-2 cells made highly tumorigenic by transfection with an activated Val-12 human Ha-ras gene or with the polyoma middle T (PyMT) oncogene, a constitutive activator of pp60 c-src tyrosine kinase activity. Compared with control vectortransfected Caco-2 cells, both oncogene-transfected cell lines exhibited: (i) decreased constitutive NF-kB DNAbinding activity and NF-kB-mediated reporter gene expression, without alteration of their response to TNF-a for activation of these parameters; (ii) reduced NF-kB cytosolic stores along with a decreased p65 expression due, at least in part, to destabilization of p65 mRNA; (iii) a decrease in adhesion to extracellular matrix component-coated substrata which was partially corrected when stimulating NF-kB transcriptional activity with TNF-a. These results indicate that the tumorigenic progression induced by oncogenic p21 ras or PyMT/pp60 c-src in human colonic Caco-2 cells is associated with a down-regulation of p65 expression and NF-kB activity which could be responsible for the reduced adhesive properties of these cells after oncogene transfection.

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Structure, Regulation and Function of NF-kappaB

Cited by 2,019 publications

References 0 publications

Regulation of DNA binding by Rel/NF-κB transcription factors: structural views

Regulation of DNA binding by Rel/NF-κB transcription factors: structural views

Transcriptional regulatory effects of lymphoma-associated NFKB2/lyt10 protooncogenes

Down-regulation of NF-κB activity and NF-κB p65 subunit expression by ras and polyoma middle T oncogenes in human colonic Caco-2 cells

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