ArticleCell death & disease2022
SUMOylation of PDPK1 Is required to maintain glycolysis-dependent CD4 T-cell homeostasis.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 20 citations in OpenAlex.
- Post-translational modifications in metabolic reprogramming: implications for metabolic therapy and immunotherapy in cancer.Signal transduction and targeted therapy · 2026Review
- SUMOylation is destined for regulatory T cell-related immune dysregulation.Cell death discovery · 2026Review
- Emerging role of SETD2 in the development and function of immune cells.Genes & diseases · 2025Review
- Immune regulation by the SUMO family.Nature reviews. Immunology · 2025Review
- The intersection of epigenetics and immune thrombocytopenia: new insights into disease mechanisms and treatments.Molecular biology reports · 2025Review
- An Integrated Machine Learning Framework for Developing and Validating a Diagnostic Model of Hub Genes Related to Lipid Metabolism in Chronic Rhinosinusitis.Journal of inflammation research · 2025Article
- Post-translational modifications orchestrate mTOR-driven cell death in cardiovascular disease.Frontiers in cardiovascular medicine · 2025Review
- Unraveling the critical role of SUMOylation in the governing of tumor immunity.Frontiers in immunology · 2025Review
- Post-Translational Modifications of RNA-Modifying Proteins in Cellular Dynamics and Disease Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Review
- PDIA3 orchestrates effector T cell program by serving as a chaperone to facilitate the non-canonical nuclear import of STAT1 and PKM2.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- GSK2334470 attenuates high salt-exacerbated rheumatoid arthritis progression by restoring Th17/Treg homeostasis.iScience · 2024Article
- Tissue adaptation to metabolic stress: insights from SUMOylation.Frontiers in endocrinology · 2024Review
- Dysregulated gene expression of SUMO machinery components induces the resistance to anti-PD-1 immunotherapy in lung cancer by upregulating the death of peripheral blood lymphocytes.Frontiers in immunology · 2024Article
- SUMO E3 ligase MUL1 inhibits lymph node metastasis of bladder cancer by mediating mitochondrial HSPA9 translocation.International journal of biological sciences · 2024Article
- Ubc9 regulates the expression of MHC II in dendritic cells to enhance DSS-induced colitis by mediating RBPJ SUMOylation.Cell death & disease · 2023Article
- T Cell-intrinsic Immunomodulatory Effects of TAK-981 (Subasumstat), a SUMO-activating Enzyme Inhibitor, in Chronic Lymphocytic Leukemia.Molecular cancer therapeutics · 2023Article
- UBC9 deficiency enhances immunostimulatory macrophage activation and subsequent antitumor T cell response in prostate cancer.The Journal of clinical investigation · 2023Article
- Selenium Biofortification Enhanced miR167a Expression in Broccoli Extracellular Vesicles Inducing Apoptosis in Human Pancreatic Cancer Cells by Targeting IRS1.International journal of nanomedicine · 2023Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
The immune system is finely tuned to fight against infections, eradicate neoplasms, and prevent autoimmunity. Protein posttranslational modification (PTM) constitutes a molecular layer of regulation to guarantee the proper intensity of immune response. Herein, we report that UBC9-mediated protein SUMOylation plays an essential role in peripheral CD4 T-cell proliferation, but without a perceptible impact on T-cell polarization. Both conventional T-cell (Tcon) and regulatory T-cell (Treg) maintenance are differentially affected, which was likely caused by a shared deficit in cell glycolytic metabolism. Mechanistically, PDPK1 (3-phosphoinositide-dependent protein-kinase 1) was identified as a novel SUMOylation substrate, which occurred predominantly at lysine 299 (K299) located within the protein-kinase domain. Loss of PDPK1 SUMOylation impeded its autophosphorylation at serine 241 (S241), thereby leading to hypoactivation of downstream mTORC1 signaling coupled with incompetence of cell proliferation. Altogether, our results revealed a novel regulatory mechanism in peripheral CD4 T-cell homeostatic proliferation, which involves SUMOylation regulation of PDPK1-mTORC1 signaling-mediated glycolytic process.
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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.