KDM4A serves as an α-tubulin demethylase regulating microtubule polymerization and cell mitosis

Le résumé fourni par la source

Posttranslational modifications of tubulin give microtubule distinct properties to support diverse cellular functions. Trimethylation on lysine-40 of α-tubulin (α-TubK40me3) is involved in cell division and neuronal development. The “writer” (SETD2) and “reader” (PBRM1) of α-TubK40me3 have been identified. However, the “eraser” of α-TubK40me3 and the impact of α-TubK40me3 dynamic balance on cells are still unclear. Here, we report that KDM4A, a member of the histone demethylase family, binds α-tubulin through its catalytic core domain and demethylates α-tubulin. KDM4A knockout significantly enhances α-TubK40me3, inducing microtubule polymerization and mitotic defects. Furthermore, the overpolymerized microtubules and cell mitotic defects caused by KDM4A knockout are rescued by reducing α-TubK40me3 with overexpression of an α-tubulin mutant α-tubulin K40A or depolymerizing microtubules with nocodazole treatment in cells. Together, our study identifies KDM4A as an α-tubulin demethylase, and this demethylation is important for regulating microtubule polymerization and cell mitosis.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.