Cyclin E and its low molecular weight forms in @entity1 XXXX and as targets for @entity5 therapy.

@entity1 @entity10610 @entity1472 @entity0 @entity14107 @entity146 @entity5 @entity8985 @entity15308 @entity7596
The progression of a cell through the cell cycle is promoted by cyclin dependent kinases (CDKs), which are positively regulated by cyclins and negatively regulated by CDK inhibitors. D type cyclins interact with @entity8985 and @entity14107 to drive the progression of a cell through early/mid-G(1)in response to mitogen stimulation. The association of cyclin E with @entity15308 forms an active complex in late G(1) that directs entry into S-phase. S-phase progression is directed by the @entity7596 / @entity15308 complex, and the complex of @entity7596 with @entity10610 (also known as @entity10610 ) is important for G(2) phase. Lastly, cyclin B/ @entity10610 complex is necessary for the entry into mitosis. To date only one class of substrates have been identified for cyclinD- @entity8985 and - @entity14107 complexes, those belonging to pRb family of proteins, whereas the list of cyclin E- @entity15308 substrates continues to lengthen. 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 G(1)/S transition. The recent identification of key substrates for cyclin E- @entity15308 complex has increased our appreciation of how cyclin E overexpression seen in many @entity1 @entity5 can lead to genomic instability, a feature that leads the @entity5 to a more @entity146 state. In @entity0 , the identification of low molecular weight (LMW) forms of cyclin E generated specifically in @entity5 due to elastase mediated @entity1472 -terminal proteolytic processing opens new possibilities for a targeted treatment of @entity0 . These truncated forms of cyclin E have an increased cyclin E- @entity15308 kinase activity, which correlates in vivo with accelerated entry into S phase. Characterization of the biochemical properties of these LMW forms of cyclin E, in terms of substrate specificity, extent 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 @entity0 oncogenesis and help provide novels agents to target them.
