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| Status |
Public on Aug 13, 2015 |
| Title |
Foxp3 is a key downstream regulator of p53-mediated cellular senescence |
| Organisms |
Homo sapiens; Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression and ROS production and is necessary for p53-mediated senescence.
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| Overall design |
control and treated samples (human), young passage (p3) or old passage (p7) samples (mouse). Young passage (p3) or senescent passage (p11) samples (mouse)
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| Contributor(s) |
Jin D |
| Citation missing |
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| |
| Submission date |
Aug 12, 2015 |
| Last update date |
Nov 01, 2017 |
| Contact name |
Dong-Hoon Jin |
| E-mail(s) |
inno183@amc.seoul.kr
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| Phone |
82-2-3010-2643
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| Organization name |
Asan Medical Center
|
| Street address |
88 Olympicro-43gil, Songpa-gu
|
| City |
Seoul |
| ZIP/Postal code |
138-736 |
| Country |
South Korea |
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| Platforms (3) |
| GPL10904 |
Illumina HumanHT-12 V4.0 expression beadchip (gene symbol) |
| GPL11202 |
Agilent-026655 Whole Mouse Genome Microarray 4x44K v2 (Probe Name version) |
| GPL18752 |
Illumina MouseWG-6 v2.0 expression beadchip [gene symbol version] |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA292656 |
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