ArticlePloS one2017
MCK1 is a novel regulator of myo-inositol phosphate synthase (MIPS) that is required for inhibition of inositol synthesis by the mood stabilizer valproate.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Valproic acid remodels phosphatidylglycerol homeostasis and epithelial-macrophage crosstalk in inflammatory signaling.iScience · 2026Article
- Docosahexaenoic acid modulates myo-inositol and myo-inositol biosynthetic genes expression: implications for bipolar disorder.Pharmacological reports : PR · 2026Article
- Disorder-to-order active site capping regulates the rate-limiting step of the inositol pathway.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Valproate regulates inositol synthesis by reducing expression of myo-inositol-3-phosphate synthase.Scientific reports · 2023Article
- Quantification of Myoinositol in Serum by Electrochemical Detection with an Unmodified Screen-Printed Carbon Electrode.Journal of analytical methods in chemistry · 2022Article
- Regulated inositol synthesis is critical for balanced metabolism and development in Drosophila melanogaster.Biology open · 2021Article
- Transcriptional analysis of sodium valproate in a serotonergic cell line reveals gene regulation through both HDAC inhibition-dependent and independent mechanisms.The pharmacogenomics journal · 2021Article
- The Role of the UPR Pathway in the Pathophysiology and Treatment of Bipolar Disorder.Frontiers in cellular neuroscience · 2021Review
- The Biomedical Uses of Inositols: A Nutraceutical Approach to Metabolic Dysfunction in Aging and Neurodegenerative Diseases.Biomedicines · 2020Review
- A bacterial cell factory converting glucose into scyllo-inositol, a therapeutic agent for Alzheimer's disease.Communications biology · 2020Article
- Disruption ofG3 (Bethesda, Md.) · 2018Article
- Uncovering global metabolic response to cordycepin production in Cordyceps militaris through transcriptome and genome-scale network-driven analysis.Scientific reports · 2018Article
- Inositols in Insulin Signaling and Glucose Metabolism.International journal of endocrinology · 2018Review
- Nutritional and Acquired Deficiencies in Inositol Bioavailability. Correlations with Metabolic Disorders.International journal of molecular sciences · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Myo-inositol, the precursor of all inositol compounds, is essential for the viability of eukaryotes. Identifying the factors that regulate inositol homeostasis is of obvious importance to understanding cell function and the pathologies underlying neurological and metabolic resulting from perturbation of inositol metabolism. The current study identifies Mck1, a GSK3 homolog, as a novel positive regulator of inositol de novo synthesis in yeast. Mck1 was required for normal activity of myo-inositol phosphate synthase (MIPS), which catalyzes the rate-limiting step of inositol synthesis. mck1Δ cells exhibited a 50% decrease in MIPS activity and a decreased rate of incorporation of [13C6]glucose into [13C6]-inositol-3-phosphate and [13C6]-inositol compared to WT cells. mck1Δ cells also exhibited decreased growth in the presence of the inositol depleting drug valproate (VPA), which was rescued by supplementation of inositol. However, in contrast to wild type cells, which exhibited more than a 40% decrease in MIPS activity in the presence of VPA, the drug did not significantly decrease MIPS activity in mck1Δ cells. These findings indicate that VPA-induced MIPS inhibition is Mck1-dependent, and suggest a model that unifies two current hypotheses of the mechanism of action of VPA-inositol depletion and GSK3 inhibition.
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