An overview of the roles of OCT4 in coordinating the G2/M transition and the maintenance of pluripotency. At the G2/M phase, via a non-transcriptional mechanism, OCT4 can inhibit the activation of CDK1 and lead to a prolonged G2 phase, allowing for subsequent checking of genome integrity and reducing chromosomal mis-segregation. Reciprocally, CDK1 can enhance the binding of OCT4 to the CDX2 promoter and suppress its transcription, contributing to the maintenance of ESC pluripotency. Black arrows indicate positive regulation, while red bar-headed lines indicate negative regulation. CDX2, homeobox protein CDX2; CDC25, cell cycle division 25; miR, microRNA; CDK1, cyclin-dependent kinase 1; GADD45, DNA-damage-inducible protein 45; SOX2, SRY-box 2; OCT4, octamer-binding transcription factor 4.