| Gene name: | MAPKAPK5 |
| Aging type: | Accelerate |
| Aging characteristic: | Others |
| Tissue type: | Skin |
| Cell name: | MEF |
| Experiment: | SA-β-gal activity assay//Western blot |
| Description: | PRAK+/+ primary mouse skin fibroblasts (MSFs) became growth arrested and accumulated SA-β-gal upon transduction of an activated ras allele,Ha-RasV12, indicating that ras triggered premature senescence.Similarly, PRAK deletion abolished ras-induced senescence in primary mouse embryonic fibroblasts (MEFs). |
| Regulatory pathway: | RAS//P38//P53-P21 |
| R-AG-Pathway: | --//--//Activation |
| Official symbol(s): | KRAS//MAKP14//TP53-CDKN1A |
| Pathway experiment: | Western blot//Luciferase reporter assay |
| Pathway description: | Ras-induced PRAK activation was also detected in primary .Ras-and MKK3/6E-induced PRAK kinase activity was greatly reduced in both BJ and MEF cells by a specific p38 inhibitor, SB203580.This indicates that PRAK is activated by p38 during ras-induced senescence.In both BJ and wild-type MEF cells containing this p53 reporter, luciferase activity was stimulated significantly by Ha-RasV12 or MKK3E,confirming the induction of p53 transcriptional activity in senescence. The regulation of p53 activity by PRAK during senescence was confirmed by the observation that ras-induced expression of p21WAF1, an endogenous p53 target previously implicated in rasinduced senescence, was abolished in PRAK-deficient BJ and MEF cells. |
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