Cyclin E is essential for progression through the G1-phase of the cell cycle and initiation of DNA replication by interacting with and activating its catalytic partner, the
cyclin dependent kinase 2 (Cdk2). Rb, as well as Cdc6, NPAT, and
nucleophosmin, critical components of cell proliferation and DNA replication, respectively, are targets of
Cyclin E/Cdk2 phosphorylation. There are a number of putative binding sites for E2F in the
cyclin E promoter region, suggesting an E2F-dependent regulation. Skp2 and Fbw7 are novel
proteins, responsible for
ubiquitin-dependent proteolysis of
Cyclin E. The tight regulation of
cyclin E expression, both at the transcriptional level and by
ubiquitin-mediated proteolysis, indicates that it has a major role in the control of the G1- and S-phase transitions.
Cyclin E is also transcriptionally regulated during radiation-induced apoptosis of hematopoietic cells. In addition to its
biological roles, deregulated
cyclin E expression has an established role in
tumorigenesis. Cell cycle regulatory molecules, such as
cyclin E, are frequently deregulated in different types of
cancers, where overexpressed native or low molecular weight forms of
Cyclin E have a significant role in
oncogenesis. During apoptosis of hematopoietic cells,
caspase-dependent proteolysis of
Cyclin E generates a p18-Cyclin E variant. Understanding the role of
Cyclin E in apoptosis may provide a novel target, which may be effective in
cancer therapy. This review summarizes what is known about the
biological role of
cyclin E, its deregulation in
cancer, and the opportunities it may provide as a target in clinical
therapy.