Cyclin E1 [CCNE1/2460]

Cyclin E1 is a member of the cyclin E family that can associate with and activate cyclin-dependent kinase Cdk2. Expression of cyclin E1 is essential for the control of the cell cycle at the late G1 and early S phase. Ubiquination by the Cul-3 pathway and Fbw7 regulates cyclin E1 levels and is critically important in normal cells. In normal cells, cyclin E1 protein expression is tightly controlled through a combination of transcriptional and proteolytic regulatory processes. However, in many types of human tumors, cyclin E1 expression is frequently dysregulated, including overexpression, non-periodic expression relative to cell division, and generation of low molecular weight (LMW) derivatives. Several studies have consistently demonstrated that Cyclin E1 is associated with disease progression or patient survival in various malignancies including carcinomas of the breast, bladder, colon, and ovary. A recent study indicated that cyclin E amplification/overexpression is responsible for trastuzumab resistance in HER2 positive breast cancer patients.