Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Numerous studies suggest that C-ANCA are directly pathogenic in vasculitis by activating leucocytes (oxidative burst, enzyme release, endothelial cytotoxicity, etc.). We and others have shown that C-ANCA can also directly activate HUVEC, but the precise target on HUVEC is unknown. We show in this study that C-ANCA recognize various targets on the HUVEC membrane (different from PR3 in our model), leading to secondary cell activation. Polyclonal affinity-purified C-ANCA recognized targets on the unfixed endothelial membrane in fluorescent ELISA, flow cytometry, and immunoprecipitation studies. C-ANCA did not react with Fcgamma receptors. Reverse transcriptase-polymerase chain reaction (RT-PCR) experiments showed that HUVEC did not express PR3. The targets of polyclonal and monoclonal anti-PR3 antibodies on the endothelial membrane were not the same. Some epitopes were lost after trypsin-EDTA digestion and formaldehyde fixation of cells, whereas anti-PR3 targeted unfixed HUVEC. This suggests that anti-PR3 react with the endothelial membrane and recognize conformational epitopes shared with PR3. Endothelial cells may thus participate in the inflammation associated with Wegener's granulomatosis and contribute to the emergence of clinical manifestations.
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PMID:Anti-proteinase-3 (PR3) antibodies (C-ANCA) recognize various targets on the human umbilical vein endothelial cell (HUVEC) membrane. 993 66

Telomerase activity (TA) is increased in human cancers and cell lines and is thought to contribute to their immortality. High TA has been found to correlate with aggressive tumor behavior. The aim of this study was to determine whether increased TA in colorectal carcinoma (CRC) correlates with survival. Formalin-fixed and paraffin-embedded tissue sections from 82 CRC and 6 cases of benign colon with diverticulosis were immunohistochemically stained for telomerase reverse transcriptase (TRT) using the immunoperoxidase method. The percentage of positive nuclei was determined for each case. Survival analysis was performed using the Kaplan-Meier method. TRT immunoreactivity was always nuclear. In normal colonic mucosa, TRT immunoreactivity was detected in the bottom of crypts. However, in normal colon adjacent to CRC, telomerase immunoreactivity was detected throughout the length of the crypts, including the upper third, and frequently in the surface epithelium. Telomerase immunoreactivity in more than 25% of the cancer cell nuclei was associated with significantly poorer patient survival (P = 0.0081). We conclude that increased TA in CRC, as demonstrated by TRT immunostaining, is associated with poorer survival, and that TA is present in normal colonic mucosa and is increased in colonic mucosa near CRC. Additional studies with larger patient samples and multivariate analysis are needed to determine whether TRT expression is an independent prognostic factor in CRC.
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PMID:Immunohistochemical detection of telomerase reverse transcriptase in colorectal adenocarcinoma and benign colonic mucosa. 1219 19

Protein-RNA interaction plays a critical role in regulating RNA synthesis by the hepatitis C virus (HCV) RNA-dependent RNA polymerase (RdRp). RNAs of 7 nucleotides (nt) or longer had affinities 5-fold better than an RNA of 5 nt, suggesting a minimal length required for binding. To identify RNA contact sites on the HCV RdRp, a biotinylated 7-nt RNA capable of directing de novo initiation was used in a process that coupled reversible formaldehyde cross-linking, RNA affinity chromatography, and mass spectrometry. By this process, we identified 18 peptides cross-linked to the 7-nt RNA. When these identified peptides were overlaid on the three-dimensional structures of NS5B, most mapped to the fingers subdomain, connecting loops between fingers and thumb subdomains and in the putative RNA binding channel. Two of the identified peptides resided in the active site cavity of the RdRp. Recombinant HCV RdRp with single residue changes in likely RNA contact sites were generated and characterized for effects on HCV RdRp activity. Mutant proteins had significant effects on cross-linking to 7-nt RNA and reduced RNA synthesis in vitro by 2- to 20-fold compared with wild type protein. When the mutations were tested for the replication of HCV RNA in the context of the cells transfected with the HCV subgenomic replicon, all except one prevented colony formation, indicating a defect in HCV RNA replication. These biochemical and functional analyses identified a number of residues in the HCV RdRp that are important for HCV RNA synthesis.
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PMID:Functional analysis of RNA binding by the hepatitis C virus RNA-dependent RNA polymerase. 1616 71