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The transcriptional activity of NF-kappa B is stimulated upon phosphorylation of its p65 subunit on serine 276 by protein kinase A (PKA). The transcriptional coactivator CPB/p300 associates with NF-kappa B p65 through two sites, an N-terminal domain that interacts with the C-terminal region of unphosphorylated p65, and a second domain that only interacts(More)
The Toll-mediated signaling cascade using the NF-kappaB pathway has been shown to be essential for immune responses in adult Drosophila, and we recently reported that a human homolog of the Drosophila Toll protein induces various immune response genes via this pathway. We now demonstrate that signaling by the human Toll receptor employs an adaptor protein,(More)
On September 14, 2015 at 09:50:45 UTC the two detectors of the Laser Interferometer Gravitational-Wave Observatory simultaneously observed a transient gravitational-wave signal. The signal sweeps upwards in frequency from 35 to 250 Hz with a peak gravitational-wave strain of 1.0×10(-21). It matches the waveform predicted by general relativity for the(More)
NF-kappa B, which consists of two polypeptides, p50 (M(r) 50K) and p65/RelA (M(r) 65K), is thought to be a key regulator of genes involved in responses to infection, inflammation and stress. Indeed, although developmentally normal, mice deficient in p50 display functional defects in immune responses. Here we describe the generation of mice deficient in the(More)
Microsatellites are tandem repeats of simple sequence that occur abundantly and at random throughout most eukaryotic genomes. Since they are usually less than 100 bp long and are embedded in DNA with unique sequence, they can be amplified in vitro using the polymerase chain reaction. Microsatellites are easy to clone and characterize and display(More)
The 2.3-A crystal structure of the transcription factor NK-kappa B p50 homodimer bound to a palindromic kappa B site reveals that the Rel homology region folds into two distinct domains, similar to those in the immunoglobulin superfamily. The p50 dimer envelopes an undistorted B-DNA helix, making specific contacts along the 10-base-pair kappa B recognition(More)
Activation of NF-kappaB as a consequence of signaling through the Toll and IL-1 receptors is a major element of innate immune responses. We report the identification and characterization of a novel intermediate in these signaling pathways that bridges TRAF6 to MEKK-1. This adapter protein, which we have named ECSIT (evolutionarily conserved signaling(More)
Stimulation of cells with inducers of NF-kappaB such as LPS and IL-1 leads to the degradation of IkappaB-alpha and IkappaB-beta proteins and translocation of NF-kappaB to the nucleus. We now demonstrate that, besides the physical partitioning of inactive NF-kappaB to the cytosol, the transcriptional activity of NF-kappaB is regulated through phosphorylation(More)
The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (È1%) of the human genome sequence and is organized as an international consortium of computational and laboratory-based scientists working to develop and apply(More)