| Gene name: | IFNG |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | HeLa |
| Experiment: | Western blot//Immunofluorescence//BrdU assay//SA-β-gal activity assay |
| Description: | The number of DDR foci gradually increased during the treatment, accompanied by activation of the DDR kinase Chk2 (phosphorylated on threonine 68) and serine15-phosphorylation of p53, an established target of DDR kinases such as ATM. Cell proliferation was impaired, as judged from diminished numbers of BrdU-incorporating cells, with concomitant development of premature senescence-like phenotype including cell spreading, nuclear enlargement, SA-β-gal and elevated cdk inhibitors p15INK4B (p15) and p21Cip1. Enhanced cyclin A, decreased PLK-1 and cyclin B at day 14 indicated a predominant G2-phase delay/arrest. Senescence-associated promyelocytic leukemia (PML) nuclear bodies were also increased, consistent with the recognized role of IFNs in stimulation of PML expression . |
| Target gene: | NOX4//ANT2 |
| Official symbol(s): | NOX4//SLC25A5 |
| R-AG-Target gene: | --//Downregulation |
| Subcategory: | Unclear |
| Target gene experiment: | Western blot//Flow cytometry |
| Target gene description: | Indeed, a 24 h treatment of HeLa cells with IFNγ (100 U/ml) transiently activated STAT1 (not shown)and induced TGFβ secretion, SMAD2 phosphorylation, Nox1 and Nox4 expression and induction, ROS production, and the DDR and inhibited cell proliferation, all detected at day 6 after a single dose of IFNγ. This multifaceted esponse indicated that even a short-term exposure of cells to IFNγ is sufficient to trigger a cascade of events leading to cellular senescence. Downregulation of ANT2 in IFNγ-treated cells led to increased proportion of apoptotic cells compared with IFNγ treatment alone, indicating the contribution of ANT2 suppression to increased genotoxic stress. |
| Regulatory pathway: | TGFβ-SMAD |
| R-AG-Pathway: | Activation |
| Official symbol(s): | TGFB1-SMAD |
| Pathway experiment: | Western blot |
| Pathway description: | TGFβ signaling pathways detected as phosphorylated SMAD2/SMAD3 were activated by IFNγ. |
Annotation:
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