CDK10

CDK10 is a cyclin-dependent serine/threonine kinase that forms an active kinase complex with Cyclin M, the product of FAM58A, establishing CDK10 as a bona fide cyclin-dependent kinase rather than an orphan CDK^[1][2]. Mechanistically, the CDK10/Cyclin M complex phosphorylates the transcription factor ETS2 and promotes its proteasome-dependent degradation, thereby restraining ETS2-driven transcriptional programs and downstream c-RAF/MAPK signaling^[1][2]. Through this regulatory axis, CDK10 has been linked to cellular proliferation control and endocrine therapy response, because loss of CDK10 or Cyclin M increases c-RAF expression and contributes to tamoxifen resistance in breast cancer models^[1]. Beyond transcriptional regulation, CDK10/Cyclin M localizes to basal bodies and suppresses primary ciliogenesis by maintaining actin network organization through the PKN2-RhoA pathway, linking kinase activity to cytoskeletal architecture and cilium dynamics^[3][2]. In disease models, loss-of-function mutations in FAM58A disrupt Cyclin M interaction with CDK10 and are associated with STAR syndrome, a developmental disorder characterized by syndactyly, telecanthus, and anogenital and renal malformations^[1][2]. Compared with other CDK family members that primarily regulate canonical cell-cycle transitions, CDK10 is distinguished by its coordinated control of ETS2 stability, ciliogenesis, and developmental signaling pathways^[2][4].