ArticleThe EMBO journal2023
The MASTL/PP2A cell cycle kinase-phosphatase module restrains PI3K-Akt activity in an mTORC1-dependent manner.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Genome-wide CRISPR screens identify shared and context-specific regulators of podocyte resistance to oxidative injury.Renal failure · 2026Article
- CUE domain-containing 2 promotes diffuse large B-cell lymphoma progression via PP2A-B55β degradation and shapes macrophage-mediated immune responses.Molecular biomedicine · 2026Article
- Greatwall kinase regulates acute myeloid leukaemia cell division through a non-canonical mechanism.EMBO reports · 2026Article
- Integrative Transcriptomic, Network, and Genomic Analysis of Peripheral Blood Mononuclear Cells Identifies Candidate Genes Associated with Dupilumab Clinical Response in Atopic Dermatitis Patients.International journal of molecular sciences · 2026Article
- Therapeutic potential of targeting MASTL in lung adenocarcinoma.Scientific reports · 2026Article
- Regulation on the metabolic synaptic pathway in the dorsal raphe nucleus in a rat model chronic olanzapine-induced body weight gain.Frontiers in pharmacology · 2026Article
- Phosphatases in tumor cell immune escape: a perspective based on the camouflage, coercion, cytoprotection.Frontiers in cell and developmental biology · 2026Review
- PIK75 effectively reverses PI3K‒AKT activation caused by palbociclib resistance and synergistically inhibits the progression of esophageal squamous cell carcinoma.Scientific reports · 2025Article
- The balance between B55α and Greatwall expression levels predicts sensitivity to Greatwall inhibition in cancer cells.Nature communications · 2025Article
- BCAT1 Activation Reprograms Branched-Chain Amino Acid Metabolism and Epigenetically Promotes Inflammation in Diabetic Retinopathy.Investigative ophthalmology & visual science · 2025Article
- MAST Kinases' Function and Regulation: Insights from Structural Modeling and Disease Mutations.Biomedicines · 2025Article
- Article
- Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells.Life science alliance · 2025Article
- Ilicicolin C suppresses the progression of prostate cancer by inhibiting PI3K/AKT/mTOR pathway.Molecular and cellular biochemistry · 2025Article
- Development and validation of a novel signature to predict the survival and affect the immune microenvironment of esophageal squamous cell carcinoma: epigenetic-related genes.Frontiers in immunology · 2025Article
- The mLeukemia · 2024Article
- KIF2A Upregulates PI3K/AKT Signaling through Polo-like Kinase 1 (PLK1) to Affect the Proliferation and Apoptosis Levels ofBiology · 2024Article
- Treponema pallidum membrane protein Tp47 induced autophagy and inhibited cell migration in HMC3 cells via the PI3K/AKT/FOXO1 pathway.Journal of cellular and molecular medicine · 2023Article
- The diverging role of CDC14B: from mitotic exit in yeast to cell fate control in humans.The EMBO journal · 2023Review
- The MASTL/PP2A cell cycle kinase-phosphatase module restrains PI3K-Akt activity in an mTORC1-dependent manner.The EMBO journal · 2023Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The AKT-mTOR pathway is a central regulator of cell growth and metabolism. Upon sustained mTOR activity, AKT activity is attenuated by a feedback loop that restrains upstream signaling. However, how cells control the signals that limit AKT activity is not fully understood. Here, we show that MASTL/Greatwall, a cell cycle kinase that supports mitosis by phosphorylating the PP2A/B55 inhibitors ENSA/ARPP19, inhibits PI3K-AKT activity by sustaining mTORC1- and S6K1-dependent phosphorylation of IRS1 and GRB10. Genetic depletion of MASTL results in an inefficient feedback loop and AKT hyperactivity. These defects are rescued by the expression of phosphomimetic ENSA/ARPP19 or inhibition of PP2A/B55 phosphatases. MASTL is directly phosphorylated by mTORC1, thereby limiting the PP2A/B55-dependent dephosphorylation of IRS1 and GRB10 downstream of mTORC1. Downregulation of MASTL results in increased glucose uptake in vitro and increased glucose tolerance in adult mice, suggesting the relevance of the MASTL-PP2A/B55 kinase-phosphatase module in controlling AKT and maintaining metabolic homeostasis.
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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.