Deregulated cyclin E induces chromosome instability.
Cyclin E, a regulatory subunit of cyclin-dependent kinase 2 ( Cdk2), is an important regulator of entry into S phase in the mammalian cell cycle. In normal dividing cells, cyclin E accumulates at the G1/S-phase boundary and is degraded as cells progress through S phase. However, in many human tumours cyclin E is overexpressed and the levels of protein and kinase activity are often deregulated relative to the cell cycle. It is not understood how alterations in expression of cyclin E contribute to tumorigenesis. Here we show that constitutive cyclin-E overexpression in both immortalized rat embryo fibroblasts and human breast epithelial cells results in chromosome instability (CIN). In contrast, analogous expression of cyclin D1 or A does not increase the frequency of CIN. Cyclin-E-expressing cells that exhibit CIN have normal centrosome numbers. However, constitutive overexpression of cyclin E impairs S-phase progression, indicating that aberrant regulation of this process may be responsible for the CIN observed. These results indicate that downregulation of cyclin-E/ Cdk2 kinase activity following the G1/S-phase transition may be necessary for the maintenance of karyotypic stability.[1]References
- Deregulated cyclin E induces chromosome instability. Spruck, C.H., Won, K.A., Reed, S.I. Nature (1999) [Pubmed]
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