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)

The effects of suramin, an antiparasitic agent, upon in vitro hepatitis B surface antigen production by the human hepatoma cell line PLC/PRF/5 and hepatitis B virus associated DNA polymerase activity in the serum of a chronically infected patient were examined. Treatment with suramin resulted in decreases in hepatitis B surface antigen production and hepatitis B-virus associated DNA polymerase activity. The decrease in hepatitis B surface antigen production was paralleled by a general decrease in hepatoma cell viability and cellular protein synthesis. Although the inhibitory effects of suramin for hepatitis B virus appear to be nonspecific as demonstrated in these two in vitro systems, the recently announced trial of suramin for the treatment of the acquired immunodeficiency syndrome should afford an unusual opportunity to evaluate the effectiveness of suramin in the treatment of chronic hepatitis B virus infection.
 ...
PMID:Effects of suramin on in vitro HBsAg production by PLC/PRF/5 cells and hepatitis B virus DNA polymerase activity. 242 68

Primary hepatocellular carcinoma cells (PLC/342) propagated in nude mice produce hepatitis B surface antigen of subtype adr, as well as core particles containing viral DNA and DNA polymerase. Free and integrated forms of hepatitis B virus (HBV) DNA in the tumor were isolated by molecular cloning, and their nucleotide sequences were determined. Both of the two representative clones of free HBV DNA had the same genomic length (3,158 base pairs) and had two stop codons as well as two deletions in the envelope gene. None of the seven distinct clones of integrated HBV DNA possessed the entire viral genome. The integrated clone sequences had deletions and rearrangements, and only two clones possessed the envelope gene including the promoter and enhancer sequences. The C gene, which codes for core protein, was preserved in the two free clones and one of the integrated clones. The P gene, which codes for DNA polymerase, had deletions at two positions of 21 and 36 base pairs in both free clones, but was carried in toto by one of the integrated clones. The nucleotide sequences of the S genes of two free and four integrated clones, as well as their two inverted repeats, were compared. All of the eight sequences of the S gene possessed two nucleotide substitutions in common that were not displayed by any of the reported HBV genomes. The sequences differed from one another by only 1.2%. They differed, however, from 11 reported HBV genomes of subtype adr by 2.4%, from an ayr genome by 1.9%, from 2 adw genomes by 6.9%, and from 2 ayw genomes by 5.9%. These results indicate that all free and integrated HBV DNA species in the PLC/342 tumor cell evolved from a common progenitor. The free HBV DNA underwent nucleotide substitutions during several integration events, resulting in integrated HBV DNA copies that were similar in sequence but distinct from the reported HBV genomes.
 ...
PMID:Free and integrated forms of hepatitis B virus DNA in human hepatocellular carcinoma cells (PLC/342) propagated in nude mice. 366 52

The aim of our study was to isolate novel gene(s) involved in cell differentiation and embryonic liver development. Mouse cded/lior was identified from subtraction hybridization of embryonic liver cDNA libraries as well as an adult mouse liver genomic DNA library. The full open reading frame of cded/lior encodes a 131-amino acid protein with 71.88% overall similarity to the PH domain of rat PLC-gamma1. A gapped search with the C-terminal region of CDED/LIOR revealed a 36-41% similarity to several proteins related to signal transduction and cell replication, such as ORC1 and KSR. Northern blot analysis of adult mouse tissues shows a strong 2.6-kb transcript restricted to heart and skeletal muscle. RT-PCR utilizing cded/lior-specific primers demonstrates cded/lior mRNAs in heart, brain, and liver tissue throughout mid-embryonic mouse gestation. cded/lior maps to the distal end of mouse Chromosome (Chr) 2. Analysis of the genomic structure for cded/lior demonstrated a single exon gene that is not an alternatively spliced isoform of PLC-gamma1. Analysis of the cded/lior promoter region revealed a high GC-content, high ratio of CpG/GpC, multiple GC-boxes, the lack of a TATA box, CTF/NFI element, and two MyoD-MCK binding sites. These characteristics are also found in several genes important in the regulation of cell growth or DNA synthesis, such as transforming growth factor-beta1, c-Ha-ras, nerve growth factor, epidermal growth factor receptor, and DNA polymerase beta. These results suggest that cded/lior is a mesoderm/muscle-specific transcript that may be involved in the mesodermal inductive and regulatory interactions required for liver formation and embryonic development.
 ...
PMID:Genomic structure, chromosomal mapping, and muscle-specific expression of a PH domain-associated intronless gene, cded/lior. 989 36

Arsenic trioxide has recently been shown to inhibit growth and induce apoptosis in acute promyelocytic leukemia (APL), but little is known about the molecular mechanisms mediating these effects. Here we demonstrate that treatment of promonocytic U937 cells with arsenic trioxide leads to G2/M arrest which was associated with a dramatic increase in the levels of cyclin B and cyclin B-dependent kinase and apoptosis. We further show that apoptosis occurs after bcl-2 phosphorylation and caspase-3 activation followed by cleavage of PARP and PLC-gamma1 degradation and DNA fragmentation. The arsenic trioxide-induced apoptosis could be blocked by the protein synthesis inhibitor cycloheximide. In addition, pretreatment of U937 cells with the DNA polymerase inhibitor aphidicolin also blocked apoptosis, but did not cause the arrest of cells in the G2/M phase. The findings suggest that arsenic trioxide exerts its growth-inhibitory effects by modulating expression and/or activity of several key G2/M regulatory proteins. Furthermore, arsenic trioxide-mediated G2/M arrest correlates with the onset of apoptosis.
 ...
PMID:Arsenic trioxide induces G2/M growth arrest and apoptosis after caspase-3 activation and bcl-2 phosphorylation in promonocytic U937 cells. 1152 58