Cyclin E is an important cell cycle regulator and oncoprotein. In normal cells cyclin E promotes G1 to S phase transition, endoreduplication, histone biosynthesis, and DNA and centrosome replication. Cyclin E function is mitigated through interaction with the cyclin dependent kinase, Cdk2. However, cyclin E and Cdk2 knockout mice reveal Cdk2-independent functions of cyclin E such as G0 release and cell transformation. Understanding the function of cyclin E in normal cell division provides insight into the mechanisms of cyclin E-mediated tumorigenesis. In particular, deregulation of cyclin E can accelerate G1 phase, prolong S phase, and impair mitotic progression thereby abrogating proper cell division and inducing genomic instability. Cyclin E deregulation, including gene amplification, protein overaccumulation, and the generation of low molecular weight cyclin E isoforms is observed in many tumor types and may contribute to tumor pathology. Defining the regulation and function of cyclin E can help researchers better understand cancer biology and design effective cancer treatment strategies. In this review we outline the role of cyclin E in normal cells and the consequences of cyclin E deregulation in cancer.
Buy this Article