ArticleProceedings of the National Academy of Sciences of the United States of America2020
Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- JNK knockdown enhances CAR-T cell cytotoxicity through elevated NFATc1-dependent transcription in preclinical ovarian cancer models.Journal for immunotherapy of cancer · 2025Article
- Combining antigen specific T-cells with T-cell engager therapy induces a molecular signature that favors T-cell fitness.Blood immunology & cellular therapy · 2025Article
- High Fat Low Carbohydrate Diet Is Linked to CNS Autoimmunity Protection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Kombo knife combined with sorafenib in liver cancer treatment: Efficacy and safety under immune function influence.World journal of gastrointestinal oncology · 2024Article
- Article
- Flubendazole inhibits PD-1 and suppresses melanoma growth in immunocompetent mice.Journal of translational medicine · 2023Article
- Review
- Identification of immune-related genes in diagnosing atherosclerosis with rheumatoid arthritis through bioinformatics analysis and machine learning.Frontiers in immunology · 2023Article
- Mixed lineage kinase 3 and CD70 cooperation sensitize trastuzumab-resistant HER2Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mixed lineage kinase 3 requires a functional CRIB domain for regulation of blood pressure, cardiac hypertrophy, and left ventricular function.American journal of physiology. Heart and circulatory physiology · 2022Article
- MLK3 mediates impact of PKG1α on cardiac function and controls blood pressure through separate mechanisms.JCI insight · 2021Article
- Mixed Lineage Kinase 3 phosphorylates prolyl-isomerase PIN1 and potentiates GLI1 signaling in pancreatic cancer development.Cancer letters · 2021Article
- Tumor-infiltrating CD8Drug discovery today · 2021Review
- The regulatory function of mixed lineage kinase 3 in tumor and host immunity.Pharmacology & therapeutics · 2021Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Mixed lineage kinase 3 (MLK3), also known as MAP3K11, was initially identified in a megakaryocytic cell line and is an emerging therapeutic target in cancer, yet its role in immune cells is not known. Here, we report that loss or pharmacological inhibition of MLK3 promotes activation and cytotoxicity of T cells. MLK3 is abundantly expressed in T cells, and its loss alters serum chemokines, cytokines, and CD28 protein expression on T cells and its subsets. MLK3 loss or pharmacological inhibition induces activation of T cells in in vitro, ex vivo, and in vivo conditions, irrespective of T cell activating agents. Conversely, overexpression of MLK3 decreases T cell activation. Mechanistically, loss or inhibition of MLK3 down-regulates expression of a prolyl-isomerase, Ppia, which is directly phosphorylated by MLK3 to increase its isomerase activity. Moreover, MLK3 also phosphorylates nuclear factor of activated T cells 1 (NFATc1) and regulates its nuclear translocation via interaction with Ppia, and this regulates T cell effector function. In an immune-competent mouse model of breast cancer, MLK3 inhibitor increases Granzyme B-positive CD8
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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.