Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.2.1.23 (
beta-galactosidase
)
14,648
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Interferon regulatory factor 3
(
IRF3
) is a transcriptional factor that plays a crucial role in activation of innate immunity and inflammation in response to viral infection. We investigated the biological function of
IRF3
overexpressed in somatic cells such as fibroblasts and astrocytes. Similar to overexpression of oncogenic H-ras in the normal human fibroblast, overexpression of
IRF3
in human fibroblast BJ cells was shown to decrease cell growth and increase senescence-associated
beta-galactosidase
activity by activating a p53 tumor suppressor. BCNU, a DNA damage agent, further accelerated p53 function and cell death in the
IRF3
-overexpressed BJ cells compared to control BJ cells, without increased expression of
IRF3
target genes.
IRF3
failed to activate p53 function and cell growth inhibition in BJ cells downregulating p53 by RNAi-mediated p53 knockdown. Furthermore, enforced expression of
IRF3
did not show any effect of cell growth inhibition in astrocytes or embryonic fibroblasts derived from the p53(-/-) mouse. When compared to control BJ cells, BJ cells which downregulated
IRF3
by RNAi-mediated
IRF3
knockdown showed extended in vitro life span. Taken together, the present study indicates that
IRF3
should be a novel inducer of cell growth inhibition and cellular senescence through activation of p53 tumor suppressor.
...
PMID:Interferon regulatory factor 3 activates p53-dependent cell growth inhibition. 1651 54
