| Gene name: | ERRFI1 |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | 2BS |
| Experiment: | Western blot//BrdU assay//SA-β-gal activity assay//SAHF |
| Description: | The Mig-6 overexpression was confirmed by Western blot analysis in the pLVX-Mig-6 cells. The results show that the pLVX-Mig-6 cells overexpressing Mig-6 showed reduced DNA synthesis.The pLVX-Mig-6 cells displayed the flat morphology, stained positively for senescence-associated-β-galactosidase (SA- β-gal) and formed senescence-associated heterochromatin foci (SAHF) 12 days after lentiviral infection (8 days post-selection). Moreover, molecular markers of senescence, such as increased p53, p21, p16 and decreased p-Rb levels, were detected after Mig-6 overexpression. |
| Target gene: | FOXO3A |
| Official symbol(s): | FOXO3A |
| R-AG-Target gene: | -- |
| Subcategory: | Unclear |
| Target gene experiment: | Knockdown//RT-PCR//Immunobloting//Western blot |
| Target gene description: | Ly294002 treatment dramatically increased Mig-6 expression in young cells. In addition, RNA interference was used to deplete FOXO3A protein in RasV12-induced senescent cells. The amount of FOXO3A protein in the cells was reduced by at least 80% by a specific shRNA as compared with the control shRNA. FOXO3A knockdown reduced Mig-6 mRNA and protein levels in these senescent cells. Results showed that Mig-6 or FOXO3A knockdown partially restored the response of Ras-induced senescence to EGF , which was suggested by the Akt phosphorylation levels. |
| Regulatory pathway: | EGFR-ERBB |
| R-AG-Pathway: | Downregulation |
| Official symbol(s): | EGFR |
| Pathway experiment: | Western blot//SA-β-gal activity assay |
| Pathway description: | Western blot analysis showed that levels of the phosphorylated EGFR (p-EGFR) were evidently decreased,but its total expression levels were not obviously altered in the senescent cells compared with those in the young cells.Deletion of ErbB-2-binding domain did not affect the phosphorylation levels of p-EGFR,p-Akt (phosphorylated Akt) and p-Erk (phosphory-lated Erk), and greatly reduced the ability of Mig-6 to enhance SA-β-Gal staining compared with the wild-type Mig-6. The result showed that as pcDNA-EGFR amount increased, SA-β-Gal activity decreased with a dosedependence,suggesting that EGFR can an-tagonise of Mig-6 induction effect of cellular senescence.AG1478 (but not AG9)treatment resulted in the decreased EGFR phosphorylation and the increase of SA-β-Gal activity, suggesting that the suppression of ErbB signalling only can elicit a cellular senescence. Subsequently, the EGFR inhibitor AG1478 treatment resulted in the increased Mig-6 expression , but not reduced Mig-6 expression. |
Annotation:
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