ArticleCell reports2020
A WW Tandem-Mediated Dimerization Mode of SAV1 Essential for Hippo Signaling.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- SAV1 in Cooperation With FKBP52 Participates in Implantation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Reversal of MPPa-PDT Resistance in Osteosarcoma by Targeting ROCK2-Mediated Autophagy.Cell proliferation · 2026Article
- Subtype-Dependent Expression Patterns of Core Hippo Pathway Components in Thymic Epithelial Tumors (TETs): An RT-qPCR Study.Biomedicines · 2026Article
- Whole-exome sequencing reveals genomic landscape of intrahepatic cholangiocarcinoma and identifies SAV1 as a potential driver.Nature communications · 2024Article
- HPV18 E7 inhibits LATS1 kinase and activates YAP1 by degrading PTPN14.bioRxiv : the preprint server for biology · 2024Article
- Interplay of RAP2 GTPase and the cytoskeleton in Hippo pathway regulation.The Journal of biological chemistry · 2024Article
- Loss of SAV1 in Kidney Proximal Tubule Induces Maladaptive Repair after Ischemia and Reperfusion Injury.International journal of molecular sciences · 2024Article
- GRK2 mediated degradation of SAV1 initiates hyperplasia of fibroblast-like synoviocytes in rheumatoid arthritis.Acta pharmaceutica Sinica. B · 2024Article
- A Non-Canonical Hippo Pathway Represses the Expression of ΔNp63.Molecular and cellular biology · 2024Article
- The WW domain of IQGAP1 binds directly to the p110α catalytic subunit of PI 3-kinase.The Biochemical journal · 2023Article
- Non-hippo kinases: indispensable roles in YAP/TAZ signaling and implications in cancer therapy.Molecular biology reports · 2023Review
- lncRNA-FMR6 directly binds SAV1 to increase apoptosis of granulosa cells in premature ovarian failure.Journal of ovarian research · 2023Article
- Constructing a novel prognostic signature of tumor driver genes for breast cancer.American journal of translational research · 2022Article
- Self-Sustained Regulation or Self-Perpetuating Dysregulation: ROS-dependent HIF-YAP-Notch Signaling as a Double-Edged Sword on Stem Cell Physiology and Tumorigenesis.Frontiers in cell and developmental biology · 2022Review
- Molecular basis of ubiquitin-specific protease 8 autoinhibition by the WW-like domain.Communications biology · 2021Article
- Regulation of MST complexes and activity via SARAH domain modifications.Biochemical Society transactions · 2021Review
- Increasing kinase domain proximity promotes MST2 autophosphorylation during Hippo signaling.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
The canonical mammalian Hippo pathway contains a core kinase signaling cascade requiring upstream MST to form a stable complex with SAV1 in order to phosphorylate the downstream LATS/MOB complex. Though SAV1 dimerization is essential for the trans-activation of MST, the molecular mechanism underlying SAV1 dimerization is unclear. Here, we discover that the SAV1 WW tandem containing a short Pro-rich extension immediately following the WW tandem (termed as "WW12ex") forms a highly stable homodimer. The crystal structure of SAV1 WW12ex reveals that the Pro-rich extension of one subunit binds to both WW domains from the other subunit. Thus, SAV1 WW12ex forms a domain-swapped dimer instead of a WW2 homodimerization-mediated dimer. The WW12ex-mediated dimerization of SAV1 is required for the MST/SAV1 complex assembly and MST kinase activation. Finally, we show that several cancer-related SAV1 variants disrupt SAV1 dimer formation, and thus, these mutations may impair the tumor-suppression activity of SAV1.
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Registered trials
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 OpenQuestion graph.