Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.7 (DNA polymerase)
 17,007 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primer recognition proteins (PRP) are accessory proteins for DNA polymerase alpha in lagging strand DNA replication. We have previously reported that the PRP consist of a complex of two proteins identified as 3-phosphoglycerate kinase (PGK) and the protein-tyrosine kinase substrate, annexin 2 monomer. The physiological role of annexin 2 is not known. Two pools of annexin 2 exist in cells. A majority of annexin 2 is localized with the plasma membrane as a heterotetramer in association with a light chain. Monomer annexin 2 is cytosolic. The identification of annexin 2 monomer as a part of the PRP complex represents one of the physiological roles of this protein in cells. To function as PRP, annexin 2 and PGK would have to be present in the cell nucleus. To investigate whether monomer annexin 2 is indeed associated with nuclear DNA synthesis, we investigated the presence of annexin 2 and PGK in the cell nucleus. In this paper, we demonstrate the presence of annexin 2 and PGK in nuclear extracts. The nuclear fraction of these proteins represents a small subset of the total cellular pools. Immunoelectron-microscopic analyses using anti-PRP antisera demonstrate the distribution of these proteins in HeLa cell nuclei and cytoplasm. Under identical conditions, an anti-cytokeratin monoclonal antibody preferentially labels the plasma membrane without detectable intracellular staining. The distribution of annexin 2 and PGK in both nuclei and cytoplasm is similarly observed in cells from normal tissues such as freshly isolated rat hepatocytes and hamster pancreatic tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunoelectron microscopic analysis of the intracellular distribution of primer recognition proteins, annexin 2 and phosphoglycerate kinase, in normal and transformed cells. 183 52

Hepatitis B virus genome-transfected HepG2 cells (2.2.15 cells) inoculated into nude mice produced tumors within 2-8 wk. Dane particles, hepatitis B virus deoxyribonucleic acid polymerase activity, hepatitis B surface antigen, and hepatitis B e antigen were detected in the serum, and 36% of mice developed antibodies to hepatitis B core antigen. In the tumors, hepatitis B surface, core, and e antigens were observed by electron microscopy and immunoenzymatic techniques. In-situ hybridization and Southern blot analysis showed hepatitis B virus deoxyribonucleic acid in the tumor. Tumors could be propagated by injection of minced tumor tissue or of a tumor-derived cell line. Liver of tumor-bearing mice as well as sera and tissues of mice inoculated with control cell lines did not show hepatitis B virus genome or viral markers. Tumors induced by both 2.2.15 and nontransfected HepG2 cells exhibited myc oncogene protein and various hepatoma-associated antigens (alpha-fetoprotein, alpha-1-antitrypsin, alpha-1-antichymotrypsin, carcinoembryonic antigen, cytokeratin), suggesting that viral formation does not interfere with expression of these antigens. This experimental model will be helpful to study the effect of drugs on in-vivo hepatitis B virus replication and viral antigen expression.
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PMID:A nude mouse model for the in vivo production of hepatitis B virus. 229 3

Most gastrointestinal stromal tumors (GISTs) can be recognized by their monotonous cytologic features and overexpression of KIT oncoprotein. Altered morphology and loss of CD117 reactivity has been described previously after chronic imatinib treatment; however, this phenomenon has not been reported in imatinib-naive tumors. Eight patients with abrupt transition from a classic CD117-positive spindle cell GIST to an anaplastic CD117-negative tumor were investigated for underlying molecular mechanisms of tumor progression. Pathologic and molecular analysis was performed on each of the 2 components. Genomic DNA polymerase chain reaction for KIT, PDGFRA, BRAF, and KRAS hot spot mutations and fluorescence in situ hybridization for detecting KIT gene copy number alterations were performed. TP53 mutational analysis was performed in 5 cases. There were 7 men and 1 woman, with an age range of 23 to 65 years. Five of the primary tumors were located in the stomach, and 1 case each originated in the small bowel, colon, and rectum. In 3 patients, the dedifferentiated component occurred in the setting of imatinib resistance, whereas the remaining 5 occurred de novo. The dedifferentiated component had an anaplastic appearance, including 1 angiosarcomatous phenotype, with high mitotic activity and necrosis, and showed complete loss of CD117 (8/8) and CD34 (5/8) expression and de novo expression of either cytokeratin (4/8) or desmin (1/8). There was no difference in the KIT genotype between the 2 components. However, 2 imatinib-resistant tumors showed coexistence of KIT exon 11 and exon 13 mutations. Fluorescence in situ hybridization showed loss of 1 KIT gene in 3 cases and low-level amplification of KIT in 2 other cases in the CD117-negative component, compared with the CD117-positive area. TP53 mutation was identified in 1/5 cases tested, being present in both components. In summary, dedifferentiation in GIST may occur either de novo or after chronic imatinib exposure and can represent a diagnostic pitfall. This phenomenon is not related to additional KIT mutations, but might be secondary to genetic instability, either represented by loss of heterozygosity or low level of KIT amplification.
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PMID:Dedifferentiation in gastrointestinal stromal tumor to an anaplastic KIT-negative phenotype: a diagnostic pitfall: morphologic and molecular characterization of 8 cases occurring either de novo or after imatinib therapy. 2334 4