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Review
Cyclin E and Its Low Molecular Weight Forms in Human Cancer and as Targets for Cancer Therapy
Said Akli and Khandan Keyomarsi
volume 2
july/august 2003 supplementPages: S038-S047
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The tight regulation of cyclin E both at the transcriptional level and by ubiquitin-mediated proteolysis indicates that it has a major role for the control of G1/S transition. The recent identification of key substrates for cyclin E-CDK2 complex has increased our appreciation of how cyclin E overexpression seen in many human cancers can lead to genomic instability, a feature that leads the tumor to a more aggressive state. In breast cancer, the identification of low molecular weight (LMW) forms of cyclin E generated specifically in tumors due to elastase mediated amino-terminal proteolytic
processing opens new possibilities for a targeted treatment of breast cancer. These truncated forms of cyclin E have an increase cyclin E-CDK2 kinase activity, which correlates in vivo with acceleration in S phase entry. Characterization of the biochemical properties of these LMW forms of cyclin E, in terms of substrate specificity, extend of their inhibition by the CDK inhibitors of the Cip/Kip family, their sensitivity to degradation, as well as elucidating their biological activities in the whole animal should help us to better understand their role in breast cancer oncogenesis and help provide novels agents to target them.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.