Title |
YAP/TEAD–Mediated Transcription Controls Cellular Senescence
|
---|---|
Published in |
Cancer Research, June 2013
|
DOI | 10.1158/0008-5472.can-12-3793 |
Pubmed ID | |
Authors |
Qi Xie, Jing Chen, Han Feng, Shengyi Peng, Ursula Adams, Yujie Bai, Li Huang, Ji Li, Junjian Huang, Songshu Meng, Zengqiang Yuan |
Abstract |
Transcription coactivator Yes-associated protein (YAP) plays an important role in the regulation of cell proliferation and apoptosis. Here, we identify a new role of YAP in the regulation of cellular senescence. We find that the expression levels of YAP proteins decrease following the replication-induced cellular senescence in IMR90 cells. Silencing of YAP inhibits cell proliferation and induces premature senescence. In additional experiments, we observe that cellular senescence induced by YAP deficiency is TEAD- and Rb/p16/p53-dependent. Furthermore, we show that Cdk6 is a direct downstream target gene of YAP in the regulation of cellular senescence, and the expression of Cdk6 is through the YAP-TEAD complex. Ectopic expression of Cdk6 rescued YAP knockdown-induced senescence. Finally, we find that downregulation of YAP in tumor cells increases senescence in response to chemotherapeutic agents, and YAP or Cdk6 expression rescues cellular senescence. Taken together, our findings define the critical role of YAP in the regulation of cellular senescence and provide a novel insight into a potential chemotherapeutic avenue for tumor suppression. |
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Country | Count | As % |
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Norway | 1 | 50% |
Italy | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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United States | 4 | 3% |
Canada | 2 | 1% |
Italy | 1 | <1% |
China | 1 | <1% |
France | 1 | <1% |
Unknown | 134 | 94% |
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Researcher | 29 | 20% |
Student > Master | 17 | 12% |
Student > Bachelor | 10 | 7% |
Student > Doctoral Student | 6 | 4% |
Other | 21 | 15% |
Unknown | 18 | 13% |
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Biochemistry, Genetics and Molecular Biology | 39 | 27% |
Medicine and Dentistry | 18 | 13% |
Neuroscience | 5 | 3% |
Chemistry | 3 | 2% |
Other | 7 | 5% |
Unknown | 24 | 17% |