Cho, Yena Hwang, Jee Won Bedford, Mark T. Na, Dong Hee Song, Dae-Geun Kim, Su-Nam Kim, Yong Kee 2025-11-21T01:12:01Z 2025-11-21T01:12:01Z 2025-11-11 2025-10 1478-811X https://pubs.kist.re.kr/handle/201004/153583 Microtubules, composed of αβ-tubulin dimers, undergo dynamic polymerization and are fundamental to cell structure and function. In the current study, we discovered that phosphatidylinositol 3-kinase class 2α (PI3KC2α) acts as a novel regulatory factor in microtubule dynamics. Specifically, asymmetric dimethylation of PI3KC2α at the R175 residue (R175me2a) by coactivator-associated arginine methyltransferase 1 (CARM1) enhances its interaction with α-tubulin, stabilizing microtubule assembly. Furthermore, lysine Demethylase 4 A (KDM4A) serves as an arginine demethylase for PI3KC2α R175me2a. During mitosis, protein kinase C (PKC)-mediated phosphorylation of KDM4A results in its dissociation from PI3KC2α, 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 PI3KC2α R175 methylation, offering new insights into the regulatory mechanisms of mitotic progression. English BioMed Central Reversible arginine methylation of PI3KC2α controls mitotic spindle dynamics Article 10.1186/s12964-025-02419-1 1 Cell Communication and Signaling, v.23, no.1 Cell Communication and Signaling 23 1 Y scie scopus 001586845400002 2-s2.0-105017764827 Cell Biology Cell Biology Article TUBULIN PROTEIN AUTOREGULATION PHOSPHORYLATION DEGRADATION INTERACTS JMJD6 CARM1 PI3KC2 alpha Tubulin Microtubule Autoregulation Mitosis