CARM1 regulates tubulin autoregulation through PI3KC2α R175 methylation
Rattachement africain : kr, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Tubulin is crucial in several cellular processes, including intracellular organization, organelle transport, motility, and chromosome segregation. Intracellular tubulin concentration is tightly regulated by an autoregulation mechanism, in which excess free tubulin promotes tubulin mRNA degradation. However, the details of how changes in free tubulin levels initiate this autoregulation remain unclear. In this study, we identified coactivator-associated arginine methyltransferase 1 (CARM1)-phosphatidylinositol 3-kinase class 2α (PI3KC2α) axis as a novel regulator of tubulin autoregulation. CARM1 stabilizes PI3KC2α by methylating its R175 residue. Once PI3KC2α is not methylated, it becomes unstable, leading to decreased cellular levels. Loss of PI3KC2α results in the release of tetratricopeptide repeat domain 5 (TTC5), which initiates tubulin autoregulation. Thus, PI3KC2α, along with its CARM1-mediated arginine methylation, regulates the initiation of tubulin autoregulation. Additionally, disruption of the CARM1-PI3KC2α axis decreases intracellular tubulin levels, leading to a synergistic increase in the cytotoxicity of microtubule-targeting agents (MTAs). Taken together, our study demonstrates that the CARM1-PI3KC2α axis is a key regulator of TTC5-mediated tubulin autoregulation and that disrupting this axis enhances the anti-cancer activity of MTAs.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- CARM1 regulates tubulin autoregulation through PI3KC2α R175 methylation
- Date Crossref
- 05/03/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Sookmyung Women's University Muscle Physiome Research Center and Research Institute of Pharmaceutical Sciences pays non établi dans la noticeUniversité ou école supérieure
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The University of Texas MD Anderson Cancer Center Department of Epigenetics and Molecular Carcinogenesis pays non établi dans la noticeÉtablissement de santé
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Korea University of Science and Technology pays non établi dans la noticeUniversité ou école supérieure
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College of Pharmacy pays non établi dans la noticeUniversité ou école supérieure
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University of Science and Technology KIST School Division of Natural Product Applied Science pays non établi dans la noticeUniversité ou école supérieure
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Natural Products Research Institute pays non établi dans la noticeStructure de recherche
Muscle Physiome Research Center and Research Institute of Pharmaceutical Sciences — Sookmyung Women's University, Department of Epigenetics and Molecular Carcinogenesis — The University of Texas MD Anderson Cancer Center et Korea University of Science and Technology, avec 3 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.