2. Academic Validation
  3. Reversible arginine methylation of PI3KC2α controls mitotic spindle dynamics

Reversible arginine methylation of PI3KC2α controls mitotic spindle dynamics

  • Cell Commun Signal. 2025 Oct 2;23(1):409. doi: 10.1186/s12964-025-02419-1.
Yena Cho 1 2,  Jee Won Hwang 2,  Mark T Bedford 3,  Dong Hee Na 4,  Dae-Geun Song 5 6,  Su-Nam Kim 5 6,  Yong Kee Kim 7 8
Affiliations

Affiliations

  • 1 Muscle Physiome Research Center, Research Institute of Pharmaceutical Sciences, Sookmyung Women's University, Seoul, 04310, Republic of Korea.
  • 2 College of Pharmacy, Sookmyung Women's University, Seoul, 04310, Republic of Korea.
  • 3 Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • 4 College of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea.
  • 5 Natural Products Research Institute, KIST Gangneung, Gangneung, 25451, Republic of Korea.
  • 6 Natural Product Applied Science, KIST School, University of Science and Technology, Gangneung, 25451, Republic of Korea.
  • 7 Muscle Physiome Research Center, Research Institute of Pharmaceutical Sciences, Sookmyung Women's University, Seoul, 04310, Republic of Korea. yksnbk@sookmyung.ac.kr.
  • 8 College of Pharmacy, Sookmyung Women's University, Seoul, 04310, Republic of Korea. yksnbk@sookmyung.ac.kr.
PMID: 41039590 DOI: 10.1186/s12964-025-02419-1
Abstract

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.

Keywords

Autoregulation; CARM1; Microtubule; Mitosis; PI3KC2α; Tubulin.

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