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 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 stimu...

Full description

Saved in:
Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2020-01, Vol.9 (1), p.171
Main Authors: Miyajima, Chiharu, Kawarada, Yuki, Inoue, Yasumichi, Suzuki, Chiaki, Mitamura, Kana, Morishita, Daisuke, Ohoka, Nobumichi, Imamura, Takeshi, Hayashi, Hidetoshi
Format: Article
Language:English
Subjects:
Acetylation
Antibodies
Apoptosis
Breast cancer
Cancer
Cell cycle
Cell growth
Cell Line
Cell proliferation
Cellular Senescence
Cloning
DNA - metabolism
DNA methylation
E1A-Associated p300 Protein - metabolism
Fibroblasts - metabolism
Gene expression
Humans
Models, Biological
Mutation
oncogene
p300
p53
p53 Protein
Plasmids
Protein Binding
Proteins
Senescence
taz
Trans-Activators - metabolism
Transcription
Transcription, Genetic
Tumor suppressor genes
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - metabolism
Tumorigenesis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Transcriptional coactivator with a PDZ-binding motif (TAZ) is one of the mammalian orthologs of 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.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells9010171