Multiple nuclear factors interact with the immunoglobulin enhancer sequences

Sen, Ranjan; Baltimore, David

doi:10.1016/0092-8674(86)90346-6

Cited by 2,539 publications

(1,564 citation statements)

References 40 publications

Supporting

Mentioning

1,510

Contrasting

Unclassified

Order By: Relevance

“…Most kB sites appear to be 10 bp in length with the consensus sequence 5 0 -GGGRN W YYCC-3 0 (where R denotes a purine base, N denotes any base, W denotes an adenine or thymine and Y denotes a pyrimidine base) (Sen and Baltimore, 1986;Chen and Ghosh, 1999). However, this degenerate kB DNA consensus sequence may still be more restrictive than what may be revealed by systematic in vitro (Linnell et al, 2004) and in vivo (Martone et al, 2003;Schreiber et al, 2006) studies.…”

Section: Dna Target Sites Of Nf-kb Dimersmentioning

confidence: 99%

Transcriptional regulation via the NF-κB signaling module

2006

View full text Add to dashboard Cite

Stimulus-induced nuclear factor-jB (NF-jB) activity, the central mediator of inflammatory responses and immune function, comprises a family of dimeric transcription factors that regulate diverse gene expression programs consisting of hundreds of genes. A family of inhibitor of jB (IjB) proteins controls NF-jB DNA-binding activity and nuclear localization. IjB protein metabolism is intricately regulated through stimulus-induced degradation and feedback re-synthesis, which allows for dynamic control of NF-jB activity. This network of interactions has been termed the NF-jB signaling module. Here, we summarize the current understanding of the molecular structures and biochemical mechanisms that determine NF-jB dimer formation and the signal-processing characteristics of the signaling module. We identify NF-jB-jB site interaction specificities and dynamic control of NF-jB activity as mechanisms that generate specificity in transcriptional regulation. We discuss examples of gene regulation that illustrate how these mechanisms may interface with other transcription regulators and promoter-associated events, and how these mechanisms suggest regulatory principles for NF-jB-mediated gene activation.

show abstract

Section: Dna Target Sites Of Nf-kb Dimersmentioning

confidence: 99%

Transcriptional regulation via the NF-κB signaling module

2006

View full text Add to dashboard Cite

show abstract

“…NFB was first discovered in 1986 and is responsible for the regulation of over 150 genes 230 . The activity of this transcription factor can contribute to the decision between cell survival and apoptosis and can play a crucial role in carcinogenesis.…”

Section: The Nfb Pathwaymentioning

confidence: 99%

Role of the pro-survival molecule Bfl-1 in melanoma

Hind

Carter

Harris

et al. 2015

The International Journal of Biochemistry & Cell Biology

View full text Add to dashboard Cite

Melanoma, the cancer derived from the melanocytes of the skin, is becoming an ever more common cancer in the ageing population of the developed world and displays an intrinsic resistance to current therapies. This chemo resistance makes metastatic melanoma an extremely difficult cancer to treat leading to a 5 year survival rate of just 20%. As such, it is important to unearth new potential drug targets to increase the prospects for melanoma patients.Bfl-1 is a pro-survival protein of the Bcl-2 family of apoptosis regulating proteins. It has been found to be over-expressed in a small subset of chemo resistant tumours, including melanoma. Accordingly, I characterised the molecule in melanoma cells and determined its role in protecting these cells from chemotherapy-induced apoptosis. I elucidated the expression profile and half-lives of the protein and mRNA across a panel of melanoma cell-lines and healthy melanocytes. I also confirmed, using pathway specific inhibitors, that Bfl-1 was transcriptionally regulated by the NFB pathway and concluded through pulsechase experiments that Bfl-1 protein was degraded, at least in part, by the proteasome. Subcellular fractionation and indirect immunofluorescence techniques elucidated that Bfl-1 was located mostly at the mitochondria in both resting and apoptotic cells, with a diffuse level present throughout the cytoplasm. As well as characterising the protein in both melanoma cells and healthy primary melanocytes, I determined its role in the resistance of these cells to apoptosis. Over-expressed Bfl-1 was found to protect melanoma cells from apoptosis caused by a range of chemotherapeutic agents in A375 melanoma cells, which naturally expressed very low levels of Bfl-1. Further, knock down of Bfl-1 using siRNA technology in melanoma cells revealed the dependence of these cells on Bfl-1 for their resistance to certain chemotherapeutic agents currently used in melanoma treatment, including the MEK inhibitor PD901. All together, this research contributes to our understanding of Bfl-1 and highlights it as a potentially important therapeutic target in metastatic melanoma.

show abstract

“…The ®nding that the p50/p65 heterodimer was constitutively expressed at a signi®cant level in the nucleus of Caco-2-H cells is noteworthy since this appears to be the case for only a few cell types known to display a substantial level of constitutive NF-kB activity (Sen and Baltimore, 1986;Hemar et al, 1991;Bours et al, 1994). After functional insertion of Ha-ras or PyMT oncogenes, Caco-2 cells showed reduced constitutive NF-kB activity, as indicated by the disappearance of nuclear p50/p65 heterodimer and decreased NF-kBmediated luciferase reporter gene expression in Caco-2-MT and Caco-2-T cells.…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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.

show abstract

Multiple nuclear factors interact with the immunoglobulin enhancer sequences

Cited by 2,539 publications

References 40 publications

Transcriptional regulation via the NF-κB signaling module

Transcriptional regulation via the NF-κB signaling module

Role of the pro-survival molecule Bfl-1 in melanoma

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

Contact Info

Product

Resources

About