Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer
Hypoxia is a common feature of solid tumors. As transcription factors, hypoxia-inducible factors (HIFs) are the master regulators of the hypoxic microenvironment; their target genes function in tumorigenesis and tumor development. Intriguingly, both yes-associated protein (YAP) and its paralog trans...
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doaj-6fdbeee028bb4b19890692c71dd30ddb2020-11-25T03:07:48ZengElsevierActa Pharmaceutica Sinica B2211-38352020-06-01106947960Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancerChenxi Zhao0Chenming Zeng1Song Ye2Xiaoyang Dai3Qiaojun He4Bo Yang5Hong Zhu6Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaDepartment of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, ChinaCenter for Drug Safety Evaluation and Research of Zhejiang University, Hangzhou 310058, ChinaZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaZhejiang Province Key Laboratory of Anti-Cancer Drug Research, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Corresponding author. Tel.: +86 571 882028401; fax: +86 571 88208400.Hypoxia is a common feature of solid tumors. As transcription factors, hypoxia-inducible factors (HIFs) are the master regulators of the hypoxic microenvironment; their target genes function in tumorigenesis and tumor development. Intriguingly, both yes-associated protein (YAP) and its paralog transcriptional coactivator with a PDZ-binding motif (TAZ) play fundamental roles in the malignant progression of hypoxic tumors. As downstream effectors of the mammalian Hippo pathway, YAP and/or TAZ (YAP/TAZ) are phosphorylated and sequestered in the cytoplasm by the large tumor suppressor kinase 1/2 (LATS1/2)-MOB kinase activator 1 (MOB1) complex, which restricts the transcriptional activity of YAP/TAZ. However, dephosphorylated YAP/TAZ have the ability to translocate to the nucleus where they induce transcription of target genes, most of which are closely related to cancer. Herein we review the tumor-related signaling crosstalk between YAP/TAZ and hypoxia, describe current agents and therapeutic strategies targeting the hypoxia–YAP/TAZ axis, and highlight questions that might have a potential impact in the future.http://www.sciencedirect.com/science/article/pii/S2211383519308214YAPTAZHIFsHypoxiaSolid tumor |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chenxi Zhao Chenming Zeng Song Ye Xiaoyang Dai Qiaojun He Bo Yang Hong Zhu |
spellingShingle |
Chenxi Zhao Chenming Zeng Song Ye Xiaoyang Dai Qiaojun He Bo Yang Hong Zhu Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer Acta Pharmaceutica Sinica B YAP TAZ HIFs Hypoxia Solid tumor |
author_facet |
Chenxi Zhao Chenming Zeng Song Ye Xiaoyang Dai Qiaojun He Bo Yang Hong Zhu |
author_sort |
Chenxi Zhao |
title |
Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer |
title_short |
Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer |
title_full |
Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer |
title_fullStr |
Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer |
title_full_unstemmed |
Yes-associated protein (YAP) and transcriptional coactivator with a PDZ-binding motif (TAZ): a nexus between hypoxia and cancer |
title_sort |
yes-associated protein (yap) and transcriptional coactivator with a pdz-binding motif (taz): a nexus between hypoxia and cancer |
publisher |
Elsevier |
series |
Acta Pharmaceutica Sinica B |
issn |
2211-3835 |
publishDate |
2020-06-01 |
description |
Hypoxia is a common feature of solid tumors. As transcription factors, hypoxia-inducible factors (HIFs) are the master regulators of the hypoxic microenvironment; their target genes function in tumorigenesis and tumor development. Intriguingly, both yes-associated protein (YAP) and its paralog transcriptional coactivator with a PDZ-binding motif (TAZ) play fundamental roles in the malignant progression of hypoxic tumors. As downstream effectors of the mammalian Hippo pathway, YAP and/or TAZ (YAP/TAZ) are phosphorylated and sequestered in the cytoplasm by the large tumor suppressor kinase 1/2 (LATS1/2)-MOB kinase activator 1 (MOB1) complex, which restricts the transcriptional activity of YAP/TAZ. However, dephosphorylated YAP/TAZ have the ability to translocate to the nucleus where they induce transcription of target genes, most of which are closely related to cancer. Herein we review the tumor-related signaling crosstalk between YAP/TAZ and hypoxia, describe current agents and therapeutic strategies targeting the hypoxia–YAP/TAZ axis, and highlight questions that might have a potential impact in the future. |
topic |
YAP TAZ HIFs Hypoxia Solid tumor |
url |
http://www.sciencedirect.com/science/article/pii/S2211383519308214 |
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