CARM1 S217 phosphorylation by CDK1 in late G2 phase facilitates mitotic entry.

The coactivator-associated arginine methyltransferase 1 (CARM1) functions as an epigenetic writer, however, its role in mitosis remains poorly understood. In this study, we identified CARM1 as a novel substrate of cyclin-dependent kinase 1 (CDK1) and revealed its novel function as a scaffold that regulates CDK1 stability. During interphase, CARM1 acts as an adaptor in the Cullin-1-mediated CDK1 degradation process, limiting nuclear levels of CDK1. In late G2 phase, the CDK1/Cyclin B1 complex translocates to the nucleus, where it phosphorylates the S217 residue of CARM1. This phosphorylation not only inhibits CARM1's enzymatic activity but also facilitates its translocation to the cytoplasm, leading to the loss of its scaffolding function. Consequently, the CDK1/Cyclin B1 complex resides for longer in the nucleus and initiates mitosis. In addition, depletion or inhibition of CARM1 facilitates entry into mitosis, resulting in accelerated cell growth. Overall, our findings expand the cellular functions of CARM1 beyond its enzymatic activity.