Phosphorylation

Cell cycle deregulation and genomic instability play a major role in the aberrant cell proliferation that characterizes tumorigenesis. A novel role of the cyclin e isoform cyclin e2 in these processes is reported in the manuscript " Cyclin e2 induces genomic instability by mechanisms distinct from cyclin e1 " by Caldon et al. 1 in another issue of Cell Cycle, evidence that regulation of cyclin e2 stability is uncoupled from cyclin e1 regulation in cancer cells is described in the manuscript " Differences in degradation lead to asynchro-nous expression of cyclin e1 and cyclin e2 in cancer cells " by the same research group. 2 The major role of cyclin e is promotion of G 1-to s-phase transition through Cdk2 activation. involvement in other activities such as pre-replication complexes formation 3 and centrosome duplication has also been identified for cyclin e1. 4 The cyclin e/Cdk2 complex is in part regulated by the increased expression of cyclin e in late G 1 phase 5 and its destruction by ubiquitin-mediated protea-somal degradation in s phase (reviewed in ref. 6). Due to their high sequence similarity, cyclin e1 and e2 have been regarded as functionally redundant, and where the isoforms are even considered, cyclin e1 is generally studied as the prototypic cyclin e. However, knockout mouse models have revealed tissue-specific functions in male fertility 7 and liver regen-eration. 8 in cancer, there is also evidence for cyclin e isoform-specific functions (reviewed in ref. 9). Cyclin e1 and cyclin e2 are independent prognostic indicators in different breast cancer cohorts, and unlinked co-expression of cyclin e1 and e2 has been observed in several other types of cancers, with cyclin e2 commonly associated with the relapsing forms of the disease. However, while there is strong evidence for cyclin e1 overexpression promoting tumorigenesis, there is much less evidence for cyclin e2 oncogenicity. in the first manuscript, Caldon et al. investigated the effect of breast cancer cells' over-expression of cyclin e1 and cyclin e2 on cell cycle and genomic instability. 1 similarly to e1, overexpression of cyclin e2 resulted in chromosome aberrations, but it did not prolonged the duration of mitosis and was not associated with cdh1 or increased association with p107, which are observed with cyclin e1 overex-pression. These differences suggest cyclin e1 and cyclin e2 overexpression trigger genomic instability in distinct manners, cyclin e1 possibly dependent on its ability to form complexes with cdh1 and sequester …