| Gene name: | AGO2 |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | WI-38 |
| Experiment: | SA-β-gal activity assay//EdU assay//DAPI staining |
| Description: | In AGO2-deficient cells replicative lifespan increased by ～3–4population doublings whereas E7-expressing cells showed a lifespan extension of～5–6 population doublings. In line with this finding, the fraction of AGO2- deficient cells incorporating EdU increased and senescence-associated beta-galactosidase (SA-β-Gal) activity decreased transiently when compared with shC control cells.Strikingly, AGO2-overexpressing cells induced an abrupt proliferative arrest with features of senescence as shown by a decrease in the number of cells incorporating EdU and an increase in the percentage of SAHF-positive cells. |
| Target gene: | E2F//RB1//LET-7F |
| Official symbol(s): | E2F1//RB1//LET-7F |
| R-AG-Target gene: | --//--//-- |
| Subcategory: | Unclear |
| Target gene experiment: | CHIP//Western blot//RIP |
| Target gene description: | This analysis revealed, that of the top 577 E2F-responsive promoters known at present ,320 (that is 55.5%) were occupied by AGO proteins in senescent cells, as opposed to only 77 (that is 13.3%) in control cells.To test this possibility, we first carried out co-immunoprecipitation experiments between endogenous AGO2, RB1 and HDAC1 in cellular lysates prepared from RASV12-induced senescent fibroblasts.HDAC1 and AGO2 co-immunoprecipitated with each other. Moreover, both HDAC1 and AGO2 efficiently co-immunoprecipitated RB1. Similar results were obtained in Saos-2 cells undergoing RB1- induced senescence. Consistent with the physical interaction between AGO2 and RB1,AGO2 showed partial colocalization with SAHFs at their periphery, a staining pattern that was similar for the heterochromatin marker H3K27me3 and RB1 (ref. 2) and is thus congruent with the peripheral SAHF localization of E2F-target genes.The interaction between either H3K9me2 or AGO2 and let-7f was confirmed by RNA immunoprecipitation combined with small RNA complementary DNA (srcDNA) cloning and sequencing in senescent cells. |
| Regulatory pathway: | -- |
| R-AG-Pathway: | -- |
| Pathway experiment: | -- |
| Pathway description: | -- |
Annotation:
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