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Activation of the nuclear factor kappaB (NFkappaB) transcription factor is intimately associated with its translocation from the cytoplasm to the nucleus. Using the nuclear export inhibitor leptomycin B, we demonstrate shuttling of the RELA subunit of NFkappaB and the inhibitory subunit IkappaBalpha between these two compartments in unstimulated cells.(More)
Control of mitogen-activated protein kinase (MAPK) cascades is central to regulation of many cellular responses. We describe here human tribbles homologues (Htrbs) that control MAPK activity. MAPK kinases interact with Trbs and regulate their steady state levels. Further, Trbs selectively regulate the activation of extracellular signal-regulated kinases,(More)
Hypoxia is present in several areas of malignant tumours and is thought to result from an inadequate rate of tumour angiogenesis, vascular collapse, or both. The presence and extent of these hypoxic tumour microenvironments have recently been shown to influence tumour progression by regulating both tumour cell survival and the expression of key angiogenic(More)
We have studied the dynamics of nuclear translocation during nuclear factor kappaB activation by using a p65(RELA)-enhanced green fluorescent protein (EGFP) fusion construct. Quantitation of expression levels indicates that EGFPRELA can be detected at physiological concentrations of about 60,000 molecules per cell. Stimulation of transfected fibroblasts(More)
NF-kappaB-IkappaB complex formation regulates the level and specificity of NF-kappaB activity. Quantitative analyses showed that RelA-NF-kappaB-induced IkappaBalpha binding is regulated through inhibitor retention and phosphorylation. RelA caused an increase in IkappaBalpha phosphorylation and in degradation, which was enhanced monotonically with inhibitor(More)
Type I interleukin-1 receptor is the prototype for a family of proteins, which play a central role in early responses to injury and infection. The similarity of function across the family is reflected in similarity in signaling: all members tested couple to activation of NFkappaB and stress kinases. The coupling to these pathways is mediated by a(More)
The internalization and intracellular transport of IL-1 and its receptor were examined in the murine T cell line EL-4. For 4 h after internalization intracellular 125I-IL-1 alpha remains bound to its receptor without degradation. Electron microscope autoradiography demonstrates that internalized IL-1 accumulates in purified nuclei. The IL-1 extracted from(More)
Individual-based or agent-based models have proved useful in a variety of different biological contexts. This paper presents an agent-based model using a formal computational modelling approach to model a crucial biological system--the intracellular NF-kappaB signalling pathway. The pathway is vital to immune response regulation, and is fundamental to basic(More)
Adult human skin was separated at the dermal-epidermal junction (DEJ) by 4 published methods that involved different mechanisms of action: cold 1 M salt (tissue extraction), cold trypsinization (enzymatic), induction of a suction blister (mechanical), and warm phosphate-buffered saline (protease activation). The localization of DEJ macromolecules was(More)
Host defense against infection is induced by Toll-like and interleukin (IL)-1 receptors, and controlled by the transcription factor NF-kappaB. Our earlier studies have shown that IL-1 activation impacts cytoskeletal structure and that IL-1 receptor (IL-1RI) function is substrate-dependent. Here we identify a novel regulatory component, TILRR, which(More)