ArticleProceedings of the National Academy of Sciences of the United States of America2012
Mixed-lineage kinase 3 phosphorylates prolyl-isomerase Pin1 to regulate its nuclear translocation and cellular function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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Who cites it
48 citing papers in PubMed, 76 citations in OpenAlex.
- The Effect of Prolyl Isomerase Pin1 on the Development of Metabolic Dysfunction-Associated Steatohepatitis and a New Treatment Strategy.International journal of molecular sciences · 2026Review
- Dissecting the functional behavior of the differentially phosphorylated prolyl isomerase, Pin1.Protein science : a publication of the Protein Society · 2024Article
- MYC and KRAS cooperation: from historical challenges to therapeutic opportunities in cancer.Signal transduction and targeted therapy · 2024Review
- Pin1-catalyzed conformational regulation after phosphorylation: A distinct checkpoint in cell signaling and drug discovery.Science signaling · 2024Review
- Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells.Nature communications · 2024Article
- The molecular mechanisms of peptidyl-prolylFrontiers in pharmacology · 2024Review
- Long-term normalization of calcineurin activity in model mice rescues Pin1 and attenuates Alzheimer's phenotypes without blocking peripheral T cell IL-2 response.Alzheimer's research & therapy · 2023Article
- Targeting the Cysteine Redox Proteome in Parkinson's Disease: The Role of Glutathione Precursors and Beyond.Antioxidants (Basel, Switzerland) · 2023Review
- Hepatic Pin1 Expression, Particularly in Nuclei, Is Increased in NASH Patients in Accordance with Evidence of the Role of Pin1 in Lipid Accumulation Shown in Hepatoma Cell Lines.International journal of molecular sciences · 2023Article
- Pin1 and Alzheimer's disease.Translational research : the journal of laboratory and clinical medicine · 2023Review
- Regulation of eukaryotic protein kinases by Pin1, a peptidyl-prolyl isomerase.Advances in biological regulation · 2023Article
- Review
- MAP4K4 promotes pancreatic tumorigenesis via phosphorylation and activation of mixed lineage kinase 3.Oncogene · 2021Article
- 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
- Targeting Pin1 for Modulation of Cell Motility and Cancer Therapy.Biomedicines · 2021Review
- The regulatory function of mixed lineage kinase 3 in tumor and host immunity.Pharmacology & therapeutics · 2021Review
- Cancer and Alzheimer's disease inverse relationship: an age-associated diverging derailment of shared pathways.Molecular psychiatry · 2021Review
- Coupled intra- and interdomain dynamics support domain cross-talk in Pin1.The Journal of biological chemistry · 2020Article
- Mixed lineage kinase 3 inhibition induces T cell activation and cytotoxicity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 1 country.
Funding
Abstract
Nuclear protein peptidyl-prolyl isomerase Pin1-mediated prolyl isomerization is an essential and novel regulatory mechanism for protein phosphorylation. Therefore, tight regulation of Pin1 localization and catalytic activity is crucial for its normal nuclear functions. Pin1 is commonly dysregulated during oncogenesis and likely contributes to these pathologies; however, the mechanism(s) by which Pin1 catalytic activity and nuclear localization are increased is unknown. Here we demonstrate that mixed-lineage kinase 3 (MLK3), a MAP3K family member, phosphorylates Pin1 on a Ser138 site to increase its catalytic activity and nuclear translocation. This phosphorylation event drives the cell cycle and promotes cyclin D1 stability and centrosome amplification. Notably, Pin1 pSer138 is significantly up-regulated in breast tumors and is localized in the nucleus. These findings collectively suggest that the MLK3-Pin1 signaling cascade plays a critical role in regulating the cell cycle, centrosome numbers, and oncogenesis.
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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.