| Gene name: | SIN3B |
| Aging type: | Accelerate |
| Aging characteristic: | Others |
| Tissue type: | -- |
| Cell name: | MEF |
| Experiment: | SA-β-gal activity assay//Knockdown |
| Description: | The percentage of Sin3B-/-MEFs that were positive for SA-β-gal staining was significantly lower than that of their wild-type counterparts at passage 6. This observation corroborates the noticeable differences in cell morphology after six to eight passages between Sin3B-/-and Sin3B+/+ MEFs, which appeared significantly more flat and enlarged, irrespective of the cell density. |
| Target gene: | E2F |
| Official symbol(s): | E2F1 |
| R-AG-Target gene: | -- |
| Subcategory: | Unclear |
| Target gene experiment: | CHIP |
| Target gene description: | To showthe direct role of Sin3B in mediating E2F transcriptional control, we performed chromatin immunoprecipitation experiments. We found that Sin3B is strongly and specifically enriched at E2F target promoters upon RasV12 overexpression , but not at nonrelevant promoters such as oct4 , we showed that this enrichment for heterochromatin marks at E2F target promoters upon oncogenic stress requires the presence of Sin3B. |
| Regulatory pathway: | P19-P53 |
| R-AG-Pathway: | -- |
| Official symbol(s): | IL23A-TP53 |
| Pathway experiment: | Western blot//Knockdown |
| Pathway description: | As previously reported, expression of p19ARF was induced upon transduction of activated Ras into wild-type cells . Surprisingly, in Sin3B / cells overexpressing activated Ras, the level of p19ARF protein was comparable with that detected in Sin3B+/+ cells. However, the amount of p19ARF detected in the absence of oncogenic stress was significantly higher in Sin3B -/-cells compared with Sin3B+/+ cells .Our observation that Sin3B-/- fibroblasts do not senesce upon RasV12 expression, in spite of high levels of p19ARF, strongly suggests that Sin3B functions downstream of p19ARF in oncogene-induced senescence. These results showthat, although Sin3B participates in the transcriptional repression of p19ARF under normal culture conditions, it is required for the induction of senescence upon activation of the p19ARF/p53 pathway. |
Annotation:
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