ArticleProceedings of the National Academy of Sciences of the United States of America2017
The nonreceptor tyrosine kinase c-Src attenuates SCF(β-TrCP) E3-ligase activity abrogating Taz proteasomal degradation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Crk mediates Csk-Hippo signaling independently of Yap tyrosine phosphorylation to induce cell extrusion.bioRxiv : the preprint server for biology · 2024Article
- YAP1-CPNE3 positive feedback pathway promotes gastric cancer cell progression.Cellular and molecular life sciences : CMLS · 2024Article
- Multi-Functional Regulation by YAP/TAZ Signaling Networks in Tumor Progression and Metastasis.Cancers · 2023Review
- Review
- USP1 modulates hepatocellular carcinoma progression via the Hippo/TAZ axis.Cell death & disease · 2023Article
- USP1-regulated reciprocal differentiation of Th17 cells and Treg cells by deubiquitinating and stabilizing TAZ.Cellular & molecular immunology · 2023Article
- Hypoxia Triggers TAZ Phosphorylation in Basal A Triple Negative Breast Cancer Cells.International journal of molecular sciences · 2022Article
- HMG-CoA Reductase Inhibitor Statins Activate the Transcriptional Activity of p53 by Regulating the Expression of TAZ.Pharmaceuticals (Basel, Switzerland) · 2022Article
- The deubiquitinase USP7 promotes HNSCC progression via deubiquitinating and stabilizing TAZ.Cell death & disease · 2022Article
- Trp53 controls chondrogenesis and endochondral ossification by negative regulation of TAZ activity and stability via β-TrCP-mediated ubiquitination.Cell death discovery · 2022Article
- The role of TBK1 in cancer pathogenesis and anticancer immunity.Journal of experimental & clinical cancer research : CR · 2022Review
- The mechano-sensitive response of β1 integrin promotes SRC-positive late endosome recycling and activation of Yes-associated protein.The Journal of biological chemistry · 2020Article
- TBK1 regulates YAP/TAZ and fibrogenic fibroblast activation.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- NUSAP1 Promotes Gastric Cancer Tumorigenesis and Progression by Stabilizing the YAP1 Protein.Frontiers in oncology · 2020Article
- A TAZ-AXL-ABL2 Feed-Forward Signaling Axis Promotes Lung Adenocarcinoma Brain Metastasis.Cell reports · 2019Article
- Article
- Controlling Nuclear NF-κB Dynamics by β-TrCP-Insights from a Computational Model.Biomedicines · 2019Article
- SRC tyrosine kinase activates the YAP/TAZ axis and thereby drives tumor growth and metastasis.The Journal of biological chemistry · 2019Article
- PYK2 negatively regulates the Hippo pathway in TNBC by stabilizing TAZ protein.Cell death & disease · 2018Article
- Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The polyomavirus middle T antigen (PyMT) oncogene activates the cellular nonreceptor tyrosine kinase c-Src and recruits the Hippo pathway effectors, Yap (yes-associated protein) and Taz (transcriptional coactivator with PDZ-binding motif), as key steps in oncogenesis. Yap and Taz are transcription coactivators shuttling from the cytoplasm to the nucleus. The Hippo pathway kinase Lats1/2 (large tumor suppressor homolog) reduces Yap/Taz nuclear localization and minimizes their cytoplasmic levels by facilitating their ubiquitination by the E3 ligase SCF(β-TrCP). In contrast, PyMT increases the cytoplasmic Taz level. Here we show that this unique PyMT behavior is mediated by Src. We demonstrate that PyMT-induced Src activation inhibits degradation of both wild-type and tyrosine-less Taz, ruling out Taz modification as a mechanism of escaping degradation. Instead, we found that Src attenuates the SCF(β-TrCP) E3-ligase activity in blunting Taz proteasomal degradation. The role of Src in rescuing Taz from TrCP-mediated degradation gives rise to higher cell proliferation under dense cell culture. Finally, IkB (NF-kappa-B inhibitor), a known substrate of β-TrCP, was rescued by Src, suggesting a wider effect of Src on β-TrCP substrates. These findings introduce the Src tyrosine kinase as a regulator of SCF(β-TrCP).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.