Reversible Arginine Methylation of PI3KC2α Controls Mitotic Spindle Dynamics

Authors

Yena Cho
Jee Won Hwang
Mark T Bedford
Dong Hee Na
Dae-Geun Song
Su-Nam Kim
Yong Kee Kim

Language

English

Publication Date

10-2-2025

Journal

Cell Communication and Signaling

DOI

10.1186/s12964-025-02419-1

PMID

41039590

PMCID

PMC12492571

PubMedCentral® Posted Date

10-2-2025

PubMedCentral® Full Text Version

Post-print

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

Arginine, Methylation, Spindle Apparatus, Protein-Arginine N-Methyltransferases, Humans, Microtubules, Jumonji Domain-Containing Histone Demethylases, Mitosis, Phosphorylation, HeLa Cells, Protein Kinase C, Tubulin, Phosphatidylinositol 3-Kinases

Published Open-Access

yes

Recommended Citation

Cho, Yena; Hwang, Jee Won; Bedford, Mark T; et al., "Reversible Arginine Methylation of PI3KC2α Controls Mitotic Spindle Dynamics" (2025). Faculty, Staff and Student Publications. 5342.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/5342