Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.13.3 (histidine kinase)
 2,405 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many bacterial signaling pathways involve a two-component design. In these pathways, a sensor kinase, when activated by a signal, phosphorylates its own histidine, which then serves as a phosphoryl donor to an aspartate in a response regulator protein. The Sln1 protein of the yeast Saccharomyces cerevisiae has sequence similarities to both the histidine kinase and the response regulator proteins of bacteria. A missense mutation in SLN1 is lethal in the absence but not in the presence of the N-end rule pathway, a ubiquitin-dependent proteolytic system. The finding of SLN1 demonstrates that a mode of signal transduction similar to the bacterial two-component design operates in eukaryotes as well.
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PMID:A yeast protein similar to bacterial two-component regulators. 821 Nov 79

In Saccharomyces cerevisiae, a phosphorelay signal transduction pathway composed of Sln1p, Ypd1p, and Ssk1p, which are homologous to bacterial two-component signal transducers, is involved in the osmosensing mechanism. In response to high osmolarity, the phosphorelay system is inactivated and Ssk1p remains unphosphorylated. Unphosphorylated Ssk1p binds to and activates the Ssk2p mitogen-activated protein (MAP) kinase kinase kinase, which in turn activates the downstream components of the high-osmolarity glycerol response (HOG) MAP kinase cascade. Here, we report a novel inactivation mechanism for Ssk1p involving degradation by the ubiquitin-proteasome system. Degradation is regulated by the phosphotransfer from Ypd1p to Ssk1p, insofar as unphosphorylated Ssk1p is degraded more rapidly than phosphorylated Ssk1p. Ubc7p/Qri8p, an endoplasmic reticulum-associated ubiquitin-conjugating enzyme, is involved in the phosphorelay-regulated degradation of Ssk1p. In ubc7Delta cells in which the degradation is hampered, the dephosphorylation and/or inactivation process of the Hog1p MAP kinase is delayed compared with wild-type cells after the hyperosmotic treatment. Our results indicate that unphosphorylated Ssk1p is selectively degraded by the Ubc7p-dependent ubiquitin-proteasome system and that this mechanism downregulates the HOG pathway after the completion of the osmotic adaptation.
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PMID:Phosphorelay-regulated degradation of the yeast Ssk1p response regulator by the ubiquitin-proteasome system. 1294 90

This investigation aims to study the effect of curcumin on the proliferation, cycle arrest, and apoptosis of Epstein-Barr virus- (EBV-) positive nasopharyngeal carcinoma (NPC) cells. EBV+ NPC cells were subjected to curcumin treatment. The cell viability was evaluated with the CCK-8. Cell cycle and apoptosis were analyzed by flow cytometry analysis. Expression (protein and mRNA) levels were detected with western blotting and quantitative real-time PCR, respectively. Curcumin efficiently reduced the viability of EBV+ NPC cells. Curcumin induced the cycle arrest of the HONE1 and HK1-EBV cells positive for EBV. Moreover, curcumin treatment promoted the NPC cell apoptosis, via the mitochondria- and death receptor-mediated pathways. Furthermore, curcumin decreased the expression of EBNA1 in the HONE1 and HK1-EBV cells and inhibited the transcriptional level of EBNA1 in the HeLa cells. Curcumin induced EBNA1 degradation via the proteasome-ubiquitin pathway. In addition, curcumin inhibited the proliferation of HONE1 and HK1-EBV cells positive for EBV, probably by decreasing the expression level of EBNA1. In both the HONE1 and HK1-EBV cells, curcumin inhibited the EBV latent and lytic replication. Curcumin could reduce the EBNA1 expression and exert antitumor effects against NPC in vitro.
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PMID:Curcumin Inhibits Proliferation of Epstein-Barr Virus-Associated Human Nasopharyngeal Carcinoma Cells by Inhibiting EBV Nuclear Antigen 1 Expression. 3168 3

Ticks are major parasites of domestic livestock, wildlife, and humans. After a tick bite, diverse cutaneous manifestations initially occur in the bitten area in the host. In this study, a label-free proteomics approach was applied to identify the differentially ubiquitinated proteins (DUPs) induced by tick-bitten in the skin. In total, 113 proteins were ubiquitinated in rabbit skin during tick bitten period, among which the ubiquitination levels of 43 proteins were altered. These DUPs in skin subjected to tick-bitten were enriched in metabolic processes, immune processes, and protein degradation processes. Bioinformatic analysis suggested that tick bitten may regulate the glycolysis pathway in host skin via differential ubiquitination of GAPDH, HK1 and TPI1, while regulate the ubiquitin-proteasome system, the MHC-I and MHC-II antigen-presenting pathways, and the HIF-1 signaling pathway via differential ubiquitination of MEK1, PSMC3, PSMA6, MHC-II and PSMD1. Moreover, PSMC3, PSMA6, PSMD1 and MEK1 were demonstrated as novel targets of ubiquitination. This study provides the first overview of ubiquitination in host skin affected by tick bitten and broadens our knowledge of the molecular mechanism involved in tick bitten.
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PMID:Landscape of ubiquitination events that occur in host skin in response to tick (Haemaphysalis longicornis) bitten. 3183 45