Double edge: CDK2AP1 in cell-cycle regulation and epigenetic regulation.

ABSTRACT

Cancer research has been devoted toward an understanding of the molecular regulation and functional significance of cell-cycle regulators in the pathogenesis and development of cancers. Cyclin-dependent Kinase 2-associated Protein 1 (CDK2AP1) is one such cell-cycle regulator, originally identified as a growth suppressor and a prognostic marker for human oral/head and neck cancers. Functional importance and the molecular mechanism of CDK2AP1-mediated cell-cycle regulation have been documented over the years. Recent progress has shown that CDK2AP1 is a competency factor in embryonic stem cell differentiation. Deletion of CDK2AP1 leads to early embryonic lethality, potentially through altered differentiation capability of embryonic stem cells. More intriguingly, CDK2AP1 exerts its effect on stem cell maintenance/differentiation through epigenetic regulation. Cancer cells and stem cells share common cellular characteristics, most prominently in maintaining high proliferative potential through an unconventional cell-cycle regulatory mechanism. Cross-talk between cellular processes and molecular signaling pathways is frequent in any biological system. Currently, it remains largely elusive how cell-cycle regulation is mechanistically linked to epigenetic control. Understanding the molecular mechanism underlying CDK2AP1-mediated cell-cycle regulation and epigenetic control will set an example for establishing a novel and effective molecular link between these two important regulatory mechanisms.