ScholarWorks@숙명여자대학교

초록

Microtubules, composed of alpha beta-tubulin dimers, undergo dynamic polymerization and are fundamental to cell structure and function. In the current study, we discovered that phosphatidylinositol 3-kinase class 2 alpha (PI3KC2 alpha) acts as a novel regulatory factor in microtubule dynamics. Specifically, asymmetric dimethylation of PI3KC2 alpha at the R175 residue (R175me2a) by coactivator-associated arginine methyltransferase 1 (CARM1) enhances its interaction with alpha-tubulin, stabilizing microtubule assembly. Furthermore, lysine Demethylase 4 A (KDM4A) serves as an arginine demethylase for PI3KC2 alpha R175me2a. During mitosis, protein kinase C (PKC)-mediated phosphorylation of KDM4A results in its dissociation from PI3KC2 alpha, preventing demethylation and increasing R175me2a levels. This facilitates spindle formation and highlights the critical role of reversible arginine methylation in regulating mitotic spindle dynamics. Cumulatively, these findings reveal the coordinated interplay between CARM1 and KDM4A in modulating microtubule behavior through PI3KC2 alpha R175 methylation, offering new insights into the regulatory mechanisms of mitotic progression.

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