Transcriptional Coactivator TAZ Negatively Regulates Tumor Suppressor p53 Activity and Cellular Senescence

Autor: Chiharu Miyajima, Yuki Kawarada, Yasumichi Inoue, Chiaki Suzuki, Kana Mitamura, Daisuke Morishita, Nobumichi Ohoka, Takeshi Imamura, Hidetoshi Hayashi
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cells, Vol 9, Iss 1, p 171 (2020)
Druh dokumentu: article
ISSN: 2073-4409
DOI: 10.3390/cells9010171
Popis: Transcriptional coactivator with a PDZ-binding motif (TAZ) is one of the mammalian orthologs of Drosophila 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.
Databáze: Directory of Open Access Journals