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Mammalian cells concentrate Golgi membranes around the centrosome in a microtubule-dependent manner. The mechanisms involved in generating a single Golgi ribbon in the periphery of the centrosome remain unknown. Here we show that GMAP-210, a cis-Golgi microtubule binding protein, recruits γ-tubulin-containing complexes to Golgi membranes even in conditions where microtubule polymerization is prevented...
report in this issue that the Golgi protein GMAP-210 is sufficient to confer pericentrosomal positioning and recruits γ-tubulin and associated microtubule-nucleating ring complex proteins to Golgi membranes. The results raise the possibility that short microtubules emanate from the Golgi to mediate its organization and positioning.
Understanding how a particular cell type expresses the lamellipodial or filopodial form of the actin machinery is essential to understanding a cell's functional interactions. To determine how a cell ''chooses'' among these alternative modes of ''molecular hardware,'' we tested the role of key proteins that affect actin filament barbed ends. Depletion of capping protein (CP) by short hairpin RNA (shRNA)...
Ubiquitylation provides a means of targeting substrate proteins for degradation by the proteasome. Novel findings in C. elegans (, this issue of Cell) establish that two ubiquitin-ligases team up to multiubiquitylate the myosin chaperone UNC-45, suggesting a novel link between regulated protein degradation and myosin assembly.
High-resolution crystal structures have highlighted functionally important regions in multisubunit RNA polymerases, including the secondary channel, or pore, which is postulated to allow the diffusion of small molecules both into and out of the active center of the enzyme. Recent work from several groups has illustrated how regulatory factors and small molecules can exploit the secondary channel to...
In yeast, hyperosmotic stress causes an immediate dissociation of most proteins from chromatin, presumably because cells are unprepared for, and initially unresponsive to, increased ion concentrations in the nucleus. Osmotic stress activates Hog1 MAP kinase, which phosphorylates at least two proteins located at the plasma membrane, the Nha1 Na + /H + antiporter and the Tok1 potassium...
Bacterial transcription is regulated by the alarmone ppGpp, which binds near the catalytic site of RNA polymerase (RNAP) and modulates its activity. We show that the DksA protein is a crucial component of ppGpp-dependent regulation. The 2.0 A resolution structure of Escherichia coli DksA reveals a globular domain and a coiled coil with two highly conserved Asp residues at its tip that is reminiscent...
Ribosomal RNA (rRNA) transcription is regulated primarily at the level of initiation from rRNA promoters. The unusual kinetic properties of these promoters result in their specific regulation by two small molecule signals, ppGpp and the initiating NTP, that bind to RNA polymerase (RNAP) at all promoters. We show here that DksA, a protein previously unsuspected as a transcription factor, is absolutely...
The G protein-coupled, receptor-activated phosphoinositide 3-kinase γ (PI3Kγ) mediates inflammatory responses and negatively controls cardiac contractility by reducing cAMP concentration. Here, we report that mice carrying a targeted mutation in the PI3Kγ gene causing loss of kinase activity (PI3Kγ KD/KD ) display reduced inflammatory reactions but no alterations in cardiac...
Epithelial-mesenchymal transitions (EMT) are vital for morphogenesis during embryonic development and are also implicated in the conversion of early stage tumors into invasive malignancies. Several key inducers of EMT are transcription factors that repress E-cadherin expression. A recent report in Cell adds Twist to this list and links EMT to the ability of breast cancer cells to enter the circulation...
The efficacy of synaptic transmission between neurons can be altered transiently during neuronal network activity. This phenomenon of short-term plasticity is a key determinant of network properties; is involved in many physiological processes such as motor control, sound localization, or sensory adaptation; and is critically dependent on cytosolic [Ca 2+ ]. However, the underlying molecular...
The organization of the motor protein myosin into motile cellular structures requires precise temporal and spatial control. Caenorhabditis elegans UNC-45 facilitates this by functioning both as a chaperone and as a Hsp90 cochaperone for myosin during thick filament assembly. Consequently, mutations in C. elegans unc-45 result in paralyzed animals with severe myofibril disorganization in striated body...
When it comes to silencing genes in mice, not all approaches are equal. An example published in this issue of Cell suggests that caution should be used when validating potential drug targets by genetic disruption
A link between inflammation and cancer has long been suspected, but its molecular nature remained ill defined. A key player in inflammation is transcription factor NF-κB whose activity is triggered in response to infectious agents and proinflammatory cytokines via the IκB kinase (IKK) complex. Using a colitis-associated cancer model, we show that although deletion of IKKβ in intestinal epithelial...
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