ArticlePLoS biology2021
The protein phosphatase PPM1A dephosphorylates and activates YAP to govern mammalian intestinal and liver regeneration.
Article in PLoS biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 27 citations in OpenAlex.
- A Bifunctional T3SS-Effector Simultaneously Cleaves Host MAP Kinase and Inhibits PPM1A Phosphatase.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Phosphatase PPP1CC Regulates the First Lineage Segregation by GAS5 in Mouse Preimplantation Embryos.Cell proliferation · 2026Article
- Disruption of the human cystin-1 myristoyl-electrostatic switch causes polycystic kidney disease that phenocopies autosomal recessive polycystic kidney disease.Kidney international · 2026Article
- PPM1A dysfunction aggravates DPN pathology through NF-κB/NLRP3/p-tau axis involving Schwann cell/DRG neuron crosstalk.Journal of translational medicine · 2026Article
- Macrophage-Derived Type 1 IFN, Renal Tubular Epithelial Cell Polyploidization, and AKI-to-CKD Transition.Journal of the American Society of Nephrology : JASN · 2025Article
- Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics.Signal transduction and targeted therapy · 2025Review
- PP1γ promotes esophageal squamous cell carcinoma progression through the PP1γ/YAP1/SOX2 axis.Frontiers in oncology · 2025Article
- Hippo/YAP signaling's multifaceted crosstalk in cancer.Frontiers in cell and developmental biology · 2025Review
- YAP/TAZ as master regulators in liver regeneration and disease: insights into mechanisms and therapeutic targets.Molecular biology reports · 2024Review
- PCYT2 inhibits epithelial-mesenchymal transition in colorectal cancer by elevating YAP1 phosphorylation.JCI insight · 2024Article
- Article
- PPP1R12A is a recycling endosomal phosphatase that facilitates YAP activation.Scientific reports · 2023Article
- Inhibition of TANK-binding kinase1 attenuates the astrocyte-mediated neuroinflammatory response through YAP signaling after spinal cord injury.CNS neuroscience & therapeutics · 2023Article
- YAP/TAZ: Molecular pathway and disease therapy.MedComm · 2023Review
- The Emerging Role of Protein Phosphatase in Regeneration.Life (Basel, Switzerland) · 2023Review
- Protein phosphatase PPM1A inhibition attenuates osteoarthritis via regulating TGF-β/Smad2 signaling in chondrocytes.JCI insight · 2023Article
- Distinct osteogenic effect of different periosteum derived cells via Hippo-YAP cascade signaling.Cell cycle (Georgetown, Tex.) · 2023Article
- Protein Phosphatase 2A with B' specificity subunits regulates the Hippo-Yorkie signaling axis in the Drosophila eye disc.Journal of cell science · 2022Article
- Applications of human organoids in the personalized treatment for digestive diseases.Signal transduction and targeted therapy · 2022Review
- Apoptosis in Type 2 Diabetes: Can It Be Prevented? Hippo Pathway Prospects.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Hippo-YAP pathway responds to diverse environmental cues to manage tissue homeostasis, organ regeneration, tumorigenesis, and immunity. However, how phosphatase(s) directly target Yes-associated protein (YAP) and determine its physiological activity are still inconclusive. Here, we utilized an unbiased phosphatome screening and identified protein phosphatase magnesium-dependent 1A (PPM1A/PP2Cα) as the bona fide and physiological YAP phosphatase. We found that PPM1A was associated with YAP/TAZ in both the cytoplasm and the nucleus to directly eliminate phospho-S127 on YAP, which conferring YAP the nuclear distribution and transcription potency. Accordingly, genetic ablation or depletion of PPM1A in cells, organoids, and mice elicited an enhanced YAP/TAZ cytoplasmic retention and resulted in the diminished cell proliferation, severe gut regeneration defects in colitis, and impeded liver regeneration upon injury. These regeneration defects in murine model were largely rescued via a genetic large tumor suppressor kinase 1 (LATS1) deficiency or the pharmacological inhibition of Hippo-YAP signaling. Therefore, we identify a physiological phosphatase of YAP/TAZ, describe its critical effects in YAP/TAZ cellular distribution, and demonstrate its physiological roles in mammalian organ regeneration.
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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 OpenQuestion graph.