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Query: EC:3.2.1.23 (
beta-galactosidase
)
14,648
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Recent studies have implicated interferon signaling in the regulation of cellular senescence. However, the role of specific interferon-inducible proteins in cellular senescence remains to be defined. Here we report that
IFI 16
, an interferon-inducible transcriptional modulator from the p200-protein family, contributes to cellular senescence of prostate epithelial cells. Normal human prostate epithelial cells (PrEC) in culture expressed detectable levels of
IFI 16
, and the levels increased more than fourfold when cells approached cellular senescence. Consistent with a role of
IFI 16
in cellular senescence, human prostate cancer cell lines either did not express
IFI 16
or expressed a variant form, which was primarily detected in the cytoplasm of prostate cancer cells and not in the nucleus. Moreover, overexpression of functional
IFI 16
in human prostate cancer cell lines inhibited colony formation. Additionally, ectopic expression of
IFI 16
in clonal prostate cancer cell lines was associated with a senescence-like phenotype, production of senescence-associated
beta-galactosidase
(a biochemical marker for cellular senescence), and reduction of S-phase cells in culture. Importantly, upregulation of p21WAF1 and inhibition of E2F-stimulated transcription accompanied inhibition of cell growth by
IFI 16
in prostate cancer cell lines. Collectively, our observations support the idea that increased levels of
IFI 16
in PrECs contribute to senescence-associated irreversible cell growth arrest.
...
PMID:Role of IFI 16, a member of the interferon-inducible p200-protein family, in prostate epithelial cellular senescence. 1289 24
Expression of the human HIN-200 family member
IFI 16
has been reported to suppress cell growth and contribute to the onset of cellular senescence. However the molecular events involved in this process have not been fully characterised. We fused
IFI 16
to the estrogen receptor ligand-binding domain to establish an inducible model for studying the molecular events that cause these phenomena. In cells induced to express the ER-
IFI 16
within the nucleus there was a decrease in cellular proliferation and concomitant growth arrest in the G1 phase of the cell cycle. Unlike previous reports, this did not appear to involve the p53-p21(WAF1/CIP1)-cdk2-pRb pathway. Following nuclear expression of ER-
IFI 16
we noted senescence-like morphological changes and expression of senescence-associated
beta-galactosidase
in growth arrested cells. Importantly, we also found a marked reduction in telomerase activity in arrested cells compared to controls. Moreover,
IFI 16
and hTERT co-localised within the nucleus and these two proteins physically interacted in vivo and in vitro. Together, these data suggest that
IFI 16
may act as an endogenous regulator of telomerase activity and, through its interaction with hTERT, contributes to the inhibition of proliferation and induces a senescence-like state.
...
PMID:Inducible activation of IFI 16 results in suppression of telomerase activity, growth suppression and induction of cellular senescence. 1988 68
