Objective Research objectives and content Progression through the mammalian cell cycle is controlled by the tightly regulated activity of cyclin-dependent kinases (cdk's). Both positive and negative regulators of these kinases classify as oncogenes and tumor suppressor genes, respectively, and dysregulation of these activities is implicated in a variety of malignancies. The novel class of cdk inhibitors appears to negatively regulate G1 phase specific cdk's and, thereby, inhibit cell cycle progression. p21 is a cdk inhibitor specifically implicated in mediation of the DNA damage checkpoint, cellular senescence, and differentiation (for review see Harper & Elledge, 1996). Since p21's very complex mode of function is not yet understood and conflicting data on its features were published my research proposal is focused on elucidating the activity of p21 in more detail under different physiological conditions. My well characterized set of newly established monoclonal antibobies to human p21 will hopefully give new insights in target preferences and function of p21 under various conditions. Presently, my major interest is p21's regulation on the level of protein stability, since my own preliminary results demonstrate a quick turnover of the protein, which is mediated by the ubiquitin-proteasome protein degradation machinery. The post-translational regulation by altered protein stability appears to be an essential control mechanism of key cell cycle regulators. Harper, W., and Elledge, S.,; Cdk inhibitors in development and cancer. Cur.Op.Gen.& Dev., 6: 56-64, 1996. Training content (objective, benefit and expected impact) Independent working conditions, a good panel of applyable methods and creative scientific discussions are basics for successful research-standards in the Department of Cell Cycle and Cancer. I expect to produce a conclusive and contributory study on p21 resulting in a Ph.D thesis after approximately three years. The quality standard of this study will be of great importance for further applications in other laboratories. Links with industry / industrial relevance (22) None. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesclinical medicineoncologynatural sciencesmathematicspure mathematicsmathematical analysisfunctional analysis Programme(s) FP4-TMR - Specific research and technological development programme in the field of the training and mobility of researchers, 1994-1998 Topic(s) 0302 - Post-doctoral research training grants TL05 - Cell Biology Call for proposal Data not available Funding Scheme RGI - Research grants (individual fellowships) Coordinator DANISH CANCER SOCIETY EU contribution No data Address Strandboulevarden 49 2100 KOEPENHAGEN Denmark See on map Total cost No data Participants (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all Not available Germany EU contribution No data Address See on map Total cost No data
