cyclin E

Human cyclin E was originally identified by complementation of a triple cln deletion in Saccharomyces cerevisiae. Following the identification of human cyclin E protein, researchers found that breast cancers and some other solid tumors exhibited both quantitative and qualitative alterations in cyclin E protein production. In particular, the alterations in cyclin E expression in breast cancer correlated with increasing stage and grade of the tumor. These results suggested that cyclin E might be useful as a prognostic marker. More recently, Geng et al generated a mouse strain in which the coding sequences for cyclin D1 was deleted and replaced with those of human cyclin E. Replacement of cyclin D1 with cyclin E rescued all phenotypic manifestations seen in the cyclin D1 deficient mice and restored normal development to cyclin D1-dependent tissues. Based on the results of these studies, it appears that cyclin E is the major downstream target of cyclin D1.In addition to functioning downstream of cyclin D1, recent studies with Xenopus egg extracts demonstrated that cyclin E localizes to the centrosome. In these studies CDK2-cyclin E activity was shown to be required for centrosome duplication during S phase. Taken together, these data suggest a mechanism that coordinates centrosome reproduction with cycles of DNA synthesis and mitosis.