| Gene name: | NBR1 |
| Aging type: | Prevent |
| Aging characteristic: |
| Tissue type: | -- |
| Cell name: | MCF-7 |
| Experiment: | Cell morphological analysis//SA-β-gal activity assay//BrdU assay//Western blot |
| Description: | In MCF-7 cells, cellular senescence was induced after NBR1 siRNA transfection, as determined by cellular morphologies, cell counts, SA-β-gal staining, BrdU incorp- oration,and expression levels of p53 and p21WAF1/CIP1(p21) proteins and IL-6 and -8 mRNAs. |
| Target gene: | P53//P21//P38 |
| Official symbol(s): | P53//P21//P38 |
| R-AG-Target gene: | --//--//Downregulation |
| Subcategory: | Unclear |
| Target gene experiment: | Western blot//SA-β-gal activity assay//Knockdown |
| Target gene description: | Cellular senescence induced by NBR1 abrogation p53- and p21-dependent. Inhibition of p53 by RNAi or pifithrin-a treatment prevented senescence. In addition, NBR1 abrogation induced senescence in p53 wild-type (WT) HCT-116 cells, but not in isogenic p53-null HCT-116 or p53-null PC3 cells. Knockdown of p21 also prevented cellular senescence .NBR1 down-regulated p38 activity in that basal and anisomycin-induced activation of p38 was enhanced by NBR1 abrogation, but was reduced by overexpression of NBR1. |
| Regulatory pathway: | ERSTRESS-ATF6A |
| R-AG-Pathway: | -- |
| Official symbol(s): | ESR1-ATF6 |
| Pathway experiment: | Knockdown//Western blot//SA-β-gal activity assay |
| Pathway description: | Knockdown of ATF6a suppressed cellular senescence, as determined by cellular morphologies, cell counts, SA-β-gal staining, and expression levels of p53 and p21 proteins .In addition, transcription by ATF6a increased after NBR1 abrogation as demonstrated by a reporter assay. BiP expression, ATF6a cleavage, eIF2a phosphorylation and X-box binding protein (XBP)1 splicing were all upregulated .Moreover, treatment with the ER stress inhibitor, salubrinal,attenuated cellular senescence. Oxidative stress triggered NBR1 abrogation-induced ER stress because the ER stress was prevented by an antioxidant (Tiron) or inhibitors of NOX (DPI and AEBSF), or by knockdown of NOX2 and -4. |
Annotation:
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