Cyclin E

E-type cyclins (cyclin E1 and cyclin E2) are expressed during the late G1 phase of the cell cycle until the end of the S-phase. The activity of cyclin E is limiting for the passage of cells through the restriction point "R" which marks a "point of no return" for cells entering the division cycle from a resting state or passing front G1 into S-phase. Expression of cyclin E is regulated on the level of gene transcription mainly by members of the E2F trrnscription factor family and by its degradation via the proteasome pathway. Cyclin E binds and activates the kinase Cdk2 and by phosphorylating its substrates, the so-called "pocket proteins", the cyclic/Cdk2 complexes initiate a cascade of events that leads to the expression of S-phase specific genes. Aside from this specific function as a regulator of S-phase-entry, cyclin E plays a direct role in the initiation of DNA replication, the control of genomic stability, and the centrosome cycle. Surprisingly, recent studies have shown that the once thought essential cyclin E is dispensable for the development of higher eukaryotes and for the mitotic division of eukaryotic cells. Nevertheless, high level cyclin E expression has been associated with the initiation or progression of different human cancers, in particular breast cancer but also leukemia, lymphoma and others. Transgenic mouse models in which cyclin E is constitutively expressed develop malignant diseases, supporting the notion of cyclin E as a dominant onco-protein. (C) 2004 Elsevier Ltd. All rights reserved.