Topic
TEAD4
About: TEAD4 is a research topic. Over the lifetime, 35 publications have been published within this topic receiving 1574 citations. The topic is also known as: EFTR-2 & RTEF1.
Papers
TL;DR: It is proposed that YAP65 regulates TEAD-dependent transcription in response to mitogenic signals, and YAP 65 also binds Src/Yes protein tyrosine kinases, and the carboxy-terminal acidic activation domain in YAP is the transcriptional activation domain for TEAD transcription factors.
Abstract: Mammals express four highly conserved TEAD/TEF transcription factors that bind the same DNA sequence, but serve different functions during development. TEAD-2/TEF-4 protein purified from mouse cells was associated predominantly with a novel TEAD-binding domain at the amino terminus of YAP65, a powerful transcriptional coactivator. YAP65 interacted specifically with the carboxyl terminus of all four TEAD proteins. Both this interaction and sequence-specific DNA binding by TEAD were required for transcriptional activation in mouse cells. Expression of YAP in lymphocytic cells that normally do not support TEAD-dependent transcription (e.g., MPC11) resulted in up to 300-fold induction of TEAD activity. Conversely, TEAD overexpression squelched YAP activity. Therefore, the carboxy-terminal acidic activation domain in YAP is the transcriptional activation domain for TEAD transcription factors. However, whereas TEAD was concentrated in the nucleus, excess YAP65 accumulated in the cytoplasm as a complex with the cytoplasmic localization protein, 14-3-3. Because TEAD-dependent transcription was limited by YAP65, and YAP65 also binds Src/Yes protein tyrosine kinases, we propose that YAP65 regulates TEAD-dependent transcription in response to mitogenic signals.
738 citations
TL;DR: The transcriptional regulator YAP up-regulates Jag-1 to activate Notch signaling in HCC cells and mouse hepatocytes, suggesting the use of YAP and Notch inhibitors as therapeutics for gastrointestinal cancer.
314 citations
TL;DR: It is demonstrated that TAZ forms nuclear condensates through liquid–liquid phase separation to compartmentalize its DNA-binding cofactor TEAD4, coactivators BRD4 and MED1, and the transcription elongation factor CDK9 for transcription.
Abstract: TAZ promotes growth, development and tumorigenesis by regulating the expression of target genes. However, the manner in which TAZ orchestrates the transcriptional responses is poorly defined. Here we demonstrate that TAZ forms nuclear condensates through liquid-liquid phase separation to compartmentalize its DNA-binding cofactor TEAD4, coactivators BRD4 and MED1, and the transcription elongation factor CDK9 for transcription. TAZ forms phase-separated droplets in vitro and liquid-like nuclear condensates in vivo, and this ability is negatively regulated by Hippo signalling through LATS-mediated phosphorylation and is mediated by the coiled-coil (CC) domain. Deletion of the TAZ CC domain or substitution with the YAP CC domain prevents the phase separation of TAZ and its ability to induce the expression of TAZ-specific target genes. Thus, we identify a mechanism of transcriptional activation by TAZ and demonstrate that pathway-specific transcription factors also engage the phase-separation mechanism for efficient and specific transcriptional activation.
295 citations
TL;DR: It is shown that Tead-AP1 cooperation regulates the activity of the Dock-Rac/CDC42 module and drives the expression of a unique core set of target genes, thereby directing cell migration and invasion in cancer cells.
238 citations
TL;DR: Findings reveal a new regulatory mechanism of YAP2 by the SIRT1-mediated deacetylation that may be involved in HCC tumorigenesis and drug resistance.
Abstract: The MST/YAP (mammalian Ste20-like kinase/Yes-associated protein 2) pathway plays an important role in hepatocellular carcinoma (HCC). Although post-translational modification-especially MST/Lats (large tumor suppressor)-mediated phosphorylation and PP1 (protein phosphatase-1)-mediated dephosphorylation-has been found to regulate the activity of YAP2, very little is known about its acetylation. In our experiments, we observed that the expression of SIRT1 is significantly upregulated in the tumor samples of the hepatocarcinoma patients, and SIRT1 mRNA level positively correlates with connective tissue growth factor (CTGF) mRNA level. We then found that SIRT1 deacetylates YAP2 protein in HCC cells and SIRT1-mediated deacetylation increases the YAP2/TEAD4 association, leading to YAP2/TEAD4 transcriptional activation and upregulated cell growth in HCC cells. Moreover, knockdown of SIRT1 blocks the cisplatin (CDDP)-induced nuclear translocation of YAP2 and enhances the chemosensitivity of HCC cells to CDDP treatment. Together, our findings reveal a new regulatory mechanism of YAP2 by the SIRT1-mediated deacetylation that may be involved in HCC tumorigenesis and drug resistance.
154 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2021 | 6 |
| 2020 | 7 |
| 2019 | 7 |
| 2018 | 2 |
| 2017 | 2 |
| 2016 | 3 |