Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.26.9 (ribonuclease)
 6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effector cell protease receptor-1 (EPR-1) is a transmembrane glycoprotein receptor for factor Xa that contributes to cell surface assembly of proteolytic activities and leukocyte mitogenesis. It is now shown that membrane expression of EPR-1 is dynamically modulated by mRNA splicing. Northern hybridization analysis of EPR-1-expressing cells and genetically engineered transfectants demonstrates that this mechanism involves removal of a 451 bp intervening sequence retained in 70-90% of mature mRNA, as quantitated by polymerase chain reaction amplification and ribonuclease protection studies. Splicing of the intervening sequence occurs in a cell type-specific fashion, as judged by the constitutive membrane overexpression of EPR-1 in certain leukemic B lymphocytes and monocytic cells. Furthermore, phenotypic analysis of cell lines stably transfected with functionally spliced or unspliced EPR-1 constructs suggests a potential role of intron cis-acting sequence(s) in splicing regulation. Instead of a transmembrane receptor for factor Xa (EPR-1a), the most prevalent unspliced EPR-1 transcript generates a novel truncated protein of 110 amino acids (EPR-1b), in which a unique intron-encoded -COOH terminus carries a potential nuclear targeting signal PPQHRAKS. An antibody generated against the intron-encoded sequence of EPR-1b demonstrates prominent nuclear localization of this variant isoform in indirect immunofluorescence staining of permeabilized cells. These findings provide evidence for a novel mechanism based on high efficiency intron retention modulating factor Xa-dependent cellular effector functions.
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PMID:Splicing of effector cell protease receptor-1 mRNA is modulated by an unusual retained intron. 794 93

A major response of eukaryotic cells to the presence of unfolded proteins in the lumen of the endoplasmic reticulum (ER) is to activate genes that encode ER-located molecular chaperones, such as the binding protein. This response, called the unfolded protein response, requires the transduction of a signal from the ER to the nucleus. In yeast (Saccharomyces cerevisiae) and mammalian cells, an ER-located transmembrane receptor protein kinase/ribonuclease called Ire1, with a sensor domain in the lumen of the ER, is the first component of this pathway. Here, we report the cloning and derived amino acid sequences of AtIre1-1 and AtIre1-2, two Arabidopsis homologs of Ire1. The two proteins are located in the perinuclear ER (based on heterologous expression of fusions with green fluorescent protein). The expression patterns of the two genes (using beta-glucuronidase fusions) are nearly nonoverlapping. We also demonstrate functional complementation of the sensor domains of the two proteins in yeast and show that the Ire1-2 protein is capable of autotransphosphorylation. These and other findings are discussed in relation to the involvement of these genes in unfolded protein response signaling in plants.
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PMID:Molecular characterization of two Arabidopsis Ire1 homologs, endoplasmic reticulum-located transmembrane protein kinases. 1170 77

We studied the localization of transmembrane receptor P185(HER2) in SKOV-3 and BT-474 cancer cells by fluorescence, confocal and electron immunomicroscopy. P185(HER2) is a marker of breast and ovarian tumors, it is considered as a target for anticancer therapy. It is extremely important to choose a universal immunicytotoxic agent applicable, first, to study the distribution of P185(HER2) in cancer cells, secondly, to remove P185(HER2) from the cell surface and, thirdly, to eliminate target cells. In this work for visualization of P185HER2 We prOposed immunocytotoxic system, consisting of the monoclonal miniantibody 4D5 scFv to extracellular P185E domain fused with two molecules of barnase (ribonuclease from Bacillus amyloliquefaciens) and of its specific inhibitor barstar. Fluorescence microscopy has showed that the module 4D5 scFv-dibarnase:barstar efficiently identified P185(HER2) on the surface of cancer cells. It was revealed by confocal microscopy that interaction with 4D5 scFv-dibarnase lead to internalization of P185(HER2). The localization of P185(HER) in human ovarian carcinoma cells SKOV-3 and breast carcinoma cells BT-474 was compared by electron microscopy using 4D5 scFv-dibarnase:barstar-Au and 4D5 scFv-dibarnase-Au complexes. P185(HER) distributed on the cell surface unequally with preferential localization on protrusions or close to their bases and in contacts between protrusions and cell membrane. At 37 degrees C, P185(HER2) internalized through coated pits and vesicles and concentrated in the endosomes and multivesicular bodies in the cells of both cell lines, as well as in lysosomes in cells BT-474.
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PMID:[Immunocytochemical visualization of P185(HER2) receptor by antibody fused with dibarnase and conjugate of barstar with colloidal gold]. 2550 53