نتایج جستجو برای: proteasome
تعداد نتایج: 18078 فیلتر نتایج به سال:
A structure-based virtual screening of over 400,000 small molecules against the constitutive proteasome activity followed by in vitro assays led to the discovery of a family of proteasome inhibitors with a sulfonyl piperazine scaffold. Some members of this family of small non-peptidic inhibitors were found to act selectively on the β2 trypsin-like catalytic site with a preference for the immuno...
The proteasome is a complex multifunctional machine that destroys proteins marked for ubiquitin-mediated proteolysis. In this paper, the authors employ an elegant approach to isolate and define yeast proteasomes and their suite of interacting proteins (Verma et al., 2000). This paper has something for everyone. The method the authors developed has now become the standard in the field for rapid ...
Mitochondrial uncoupling protein 2 (UCP2) is implicated in a wide range of pathophysiological processes, including immunity and diabetes mellitus, but its rapid degradation remains uncharacterized. Using pharmacological proteasome inhibitors, immunoprecipitation, dominant negative ubiquitin mutants, [corrected] cellular fractionation and siRNA techniques, we demonstrate the involvement of the u...
Abstract pepVIII, an anticancer vaccine targeting EGFRvIII, has been tested in several trials for glioblastoma including ACT IV. a randomized Phase III trial newly diagnosed patients. While results from IV were equivocal, available data suggests the elimination of EGFRvIII was not robust. Despite its essential role antigen presentation, enhancing proteasomal processing is unexploited strategy i...
OBJECTIVE Impairment of the thrombomodulin-protein C anticoagulant pathway has been implicated in pathological thrombosis associated with malignancy. Patients who receive proteasome inhibitors as part of their chemotherapeutic regimen appear to be at decreased risk for thromboembolic events. We investigated the effects of proteasome inhibitors on endothelial thrombomodulin expression and functi...
The eukaryotic 20S proteasome is responsible for the degradation of many cellular proteins, but how it is assembled and how its distinct active sites are formed are not understood. Like other proteasome subunits, the yeast Doa3 protein is synthesized in precursor form. We show that the N-terminal propeptide is required for Doa3 incorporation into the proteasome and, remarkably, that the propept...
During an immune response, CD8+ T lymphocytes can undergo asymmetric division, giving rise to daughter cells that exhibit distinct tendencies to adopt terminal effector and memory cell fates. Here we show that "pre-effector" and "pre-memory" cells resulting from the first CD8+ T cell division in vivo exhibited low and high rates of endogenous proteasome activity, respectively. Pharmacologic red...
The 26S proteasome is known to play pivotal roles in cell-cycle progression in various eukaryotic cells; however, little is known about its role in higher plants. Here we report that the subcellular distribution of the 26S proteasome is dynamically changed in a cell-cycle dependent manner in tobacco BY-2 cells as determined by immunostaining with anti-Rpn10 (a regulatory PA700 subunit) and anti...
A major fraction of intracellular protein degradation is mediated by the proteasome. Successful degradation of these substrates requires ubiquitination and delivery to the proteasome followed by protein unfolding and disassembly of the multiubiquitin chain. Enzymes, such as Rpn11, dismantle multiubiquitin chains, and mutations can affect proteasome assembly and activity. We report that differen...
The ubiquitin-proteasome pathway is essential for long-term synaptic plasticity, but its exact roles remain unclear. Previously we established that proteasome inhibition increased the early, induction part of late-phase long-term potentiation (L-LTP) but blocks the late, maintenance part. Our prior work also showed that the proteasome modulates components of the mammalian target of rapamycin pa...
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