| Gene name: | PPARD |
| Aging type: | Accelerate |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | Primary keratinocyte |
| Gene ID: | 5467 |
| Category: | protein coding |
| Phenotype: | Skin cancer |
| Experimental category: | HL |
| PMID: | 24213576 |
| Experiment: | SA-β-gal activity assay//BrdU assay |
| Description: | A higher percentage of BrdU labeling and lower percentage of β-gal-positive cells was noted in HRAS-expressing PPARβ/δ-null compared with wild-type cells. Surprisingly, ligand activation of PPARβ/δ decreased both the percentage of β-gal- and BrdU-positive cells in HRAS-expressing wild-type but not in PPARβ/δ-null cells. |
| Target gene: | RASGRP1//ILK |
| Official symbol(s): | RASGRP1//ILK |
| R-AG-Target gene: | --//Downregulation |
| Subcategory: | Unclear |
| Target gene experiment: | Western blot//qPCR//CHIP |
| Target gene description: | Expression of the negative RAS regulator RASGAP120 was increased and the positive RAS regulator RASGRP1 was decreased in response to HRAS activation, respectively .Interestingly, expression of RASGAP120 was significantly higher, whereas expression of RASGRP1 was lower in HRAS expressing PPARβ/δ-null cells compared with wild-type cells. In response to HRAS activation, expression of mRNA encoding the negative RAS regulator Rasa4 was increased in cells from both genotypes, but relatively higher expression of Rasa4 mRNA was also observed in HRAS-expressing PPARβ/δ-null cells compared with wild-type cells (data not shown).Consistent with past studies,32 34 expression of ILK and PDPK1 was higher in control and HRAS-expressing PPARβ/δ-null cells. In silico examination of the Ilk gene revealed two potential PPREs in the second intron .Interestingly, mutating the PPARβ/δ binding half-site in a luciferase reporter construct containing the upstream PPRE abolished the repression of ILK by PPARβ/δ. |
| Regulatory pathway: | PI3K-AKT//MEK-ERK |
| R-AG-Pathway: | Downregulation//Upregulation |
| Official symbol(s): | PIK3CA-AKT1//MAP2K7-MAPK1 |
| Pathway experiment: | Western blot//SA-β-gal activity assay//Immunofluorescence//Histochemical staining//Cumulative frequency of mean intensity of cells |
| Pathway description: | The higher levels of p-MEK and p-ERK and lower level of p-AKT in wild-type cells correlated with higher markers of senescence and this was not found in HRAS-expressing PPARβ/δ-null cells . Inhibition of MEK1 with PD98059 delayed HRAS-induced senescence in both wild-type and PPARβ/δ-null cells .Higher expression of ILK, p-AKT (S473, T308) was also found in skin tumors from PPARβ/δ-null mice compared with wild-type mice. |
Annotation:
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