Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
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Query: UMLS:C0001511 (
Adhesion
)
5,955
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The Epithelial Cell
Adhesion
Molecule (EpCAM) is overexpressed in many cancers including ovarian cancer and EpCAM overexpression correlates with decreased survival of patients. It was the aim of this study to achieve a targeted methylation of the EpCAM promoter and silence EpCAM gene expression using an engineered zinc finger protein that specifically binds the EpCAM promoter fused to the catalytic domain of the Dnmt3a DNA methyltransferase. We show that transient transfection of this construct increased the methylation of the EpCAM promoter in SKOV3 cells from 4-8% in untreated cells to 30%. Up to 48% methylation was observed in stable cell lines which express the chimeric
methyltransferase
. Control experiments confirmed that the methylation was dependent on the fusion of the Zinc finger and the
methyltransferase
domains and specific for the target region. The stable cell lines with methylated EpCAM promoter showed a 60-80% reduction of EpCAM expression as determined at mRNA and protein level and exhibited a significantly reduced cell proliferation. Our data indicate that targeted methylation of the EpCAM promoter could be an approach in the therapy of EpCAM overexpressing cancers.
...
PMID:Targeted methylation of the epithelial cell adhesion molecule (EpCAM) promoter to silence its expression in ovarian cancer cells. 2448 52
Campylobacter jejuni is a bacterial pathogen that is generally acquired as a zoonotic infection from poultry and animals.
Adhesion
of C. jejuni to human colorectal epithelial cells is weakened after loss of its cj0588 gene. The Cj0588 protein belongs to the type I group of TlyA (TlyA
I
) enzymes, which 2'-O-methylate nucleotide C1920 in 23S rRNA. Slightly longer TlyA
II
versions of the
methyltransferase
are found in actinobacterial species including Mycobacterium tuberculosis, and methylate not only C1920 but also nucleotide C1409 in 16S rRNA. Loss of TlyA function attenuates virulence of both M. tuberculosis and C. jejuni. We show here that the traits impaired in C. jejuni null strains can be rescued by complementation not only with the original cj0588 (tlyA
I
) but also with a mycobacterial tlyA
II
gene. There are, however, significant differences in the recombinant phenotypes. While cj0588 restores motility, biofilm formation, adhesion to and invasion of human epithelial cells and stimulation of IL-8 production in a C. jejuni null strain, several of these properties are further enhanced by the mycobacterial tlyA
II
gene, in some cases to twice the original wild-type level. These findings strongly suggest that subtle changes in rRNA modification patterns can affect protein synthesis in a manner that has serious consequences for bacterial pathogenicity.
...
PMID:Virulence properties of Campylobacter jejuni are enhanced by displaying a mycobacterial TlyA methylation pattern in its rRNA. 3213 54
