Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular Senescence
Transcriptional coactivator with a PDZ-binding motif (TAZ) is one of the mammalian orthologs of <i>Drosophila</i> Yorkie, a transcriptional coactivator of the Hippo pathway. TAZ has been suggested to function as a regulator that modulates the expression of cell proliferation and anti-apo...
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MDPI AG
2020-01-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/1/171 |
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| author | Chiharu Miyajima Yuki Kawarada Yasumichi Inoue Chiaki Suzuki Kana Mitamura Daisuke Morishita Nobumichi Ohoka Takeshi Imamura Hidetoshi Hayashi |
| author_facet | Chiharu Miyajima Yuki Kawarada Yasumichi Inoue Chiaki Suzuki Kana Mitamura Daisuke Morishita Nobumichi Ohoka Takeshi Imamura Hidetoshi Hayashi |
| author_sort | Chiharu Miyajima |
| collection | DOAJ |
| description | Transcriptional coactivator with a PDZ-binding motif (TAZ) is one of the mammalian orthologs of <i>Drosophila</i> Yorkie, a transcriptional coactivator of the Hippo pathway. TAZ has been suggested to function as a regulator that modulates the expression of cell proliferation and anti-apoptotic genes in order to stimulate cell proliferation. TAZ has also been associated with a poor prognosis in several cancers, including breast cancer. However, the physiological role of TAZ in tumorigenesis remains unclear. We herein demonstrated that TAZ negatively regulated the activity of the tumor suppressor p53. The overexpression of TAZ down-regulated p53 transcriptional activity and its downstream gene expression. In contrast, TAZ knockdown up-regulated p21 expression induced by p53 activation. Regarding the underlying mechanism, TAZ inhibited the interaction between p53 and p300 and suppressed the p300-mediated acetylation of p53. Furthermore, TAZ knockdown induced cellular senescence in a p53-dependent manner. These results suggest that TAZ negatively regulates the tumor suppressor functions of p53 and attenuates p53-mediated cellular senescence. |
| first_indexed | 2024-03-12T19:19:29Z |
| format | Article |
| id | doaj.art-fcef14e3b77d4bfca152e1dea35c0b3d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T19:19:29Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fcef14e3b77d4bfca152e1dea35c0b3d2023-08-02T05:19:29ZengMDPI AGCells2073-44092020-01-019117110.3390/cells9010171cells9010171Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular SenescenceChiharu Miyajima0Yuki Kawarada1Yasumichi Inoue2Chiaki Suzuki3Kana Mitamura4Daisuke Morishita5Nobumichi Ohoka6Takeshi Imamura7Hidetoshi Hayashi8Department of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanDivision of Molecular Target and Gene Therapy Products, National Institute of Health Sciences, Kanagawa 210-9501, JapanDepartment of Molecular Medicine for Pathogenesis, Graduate School of Medicine, Ehime University, Ehime 791-0295, JapanDepartment of Cell Signaling, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya 467-8603, JapanTranscriptional coactivator with a PDZ-binding motif (TAZ) is one of the mammalian orthologs of <i>Drosophila</i> Yorkie, a transcriptional coactivator of the Hippo pathway. TAZ has been suggested to function as a regulator that modulates the expression of cell proliferation and anti-apoptotic genes in order to stimulate cell proliferation. TAZ has also been associated with a poor prognosis in several cancers, including breast cancer. However, the physiological role of TAZ in tumorigenesis remains unclear. We herein demonstrated that TAZ negatively regulated the activity of the tumor suppressor p53. The overexpression of TAZ down-regulated p53 transcriptional activity and its downstream gene expression. In contrast, TAZ knockdown up-regulated p21 expression induced by p53 activation. Regarding the underlying mechanism, TAZ inhibited the interaction between p53 and p300 and suppressed the p300-mediated acetylation of p53. Furthermore, TAZ knockdown induced cellular senescence in a p53-dependent manner. These results suggest that TAZ negatively regulates the tumor suppressor functions of p53 and attenuates p53-mediated cellular senescence.https://www.mdpi.com/2073-4409/9/1/171cellular senescenceoncogenep300p53taz |
| spellingShingle | Chiharu Miyajima Yuki Kawarada Yasumichi Inoue Chiaki Suzuki Kana Mitamura Daisuke Morishita Nobumichi Ohoka Takeshi Imamura Hidetoshi Hayashi Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular Senescence Cells cellular senescence oncogene p300 p53 taz |
| title | Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular Senescence |
| title_full | Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular Senescence |
| title_fullStr | Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular Senescence |
| title_full_unstemmed | Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular Senescence |
| title_short | Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular Senescence |
| title_sort | transcriptional coactivator taz negatively regulates tumor suppressor p53 activity and cellular senescence |
| topic | cellular senescence oncogene p300 p53 taz |
| url | https://www.mdpi.com/2073-4409/9/1/171 |
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