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CDK11

Study of CDK11, a protein kinase required for chromosome segregation
Funder: French National Research Agency (ANR)Project code: ANR-07-JCJC-0110
Funder Contribution: 150,000 EUR
Description

ABSTRACT: Chromosome segregation is a key process that maintains genomic stability. Defects in chromosome segregation can produce aneuploidy a phenomenon that is frequently observed in many cancer cell lines and tumours. That's why the mechanism by which the cells segregate their chromosomes is very important. Our group is highly focused on the chromosome segregation process and its regulation by phosphorylation. The CDK11(Cyclin Dependant Kinase 11), is playing a key role during mitosisand its mitotic function has first been described in our laboratory. Indeed, we demonstrated that CDK11 is required for proper cell cycle progression. Following CDK11 RNAi, the cells are blocked in mitosis and these mitotic-arrested cells show many mitotic abnormalities indicating a role for mitotic spindle organisation. This arrest also suggests that CDK11 could be a target for anti-cancer drugs in the future. We plan to continue our work on CDK11 using two different systems. First, we will analyse and select hsCDK11 interacting genes that were isolated after a yeast two hybrid screen. The most interested genes will be selected by RNAi. We also want to isolate and identify CDK11 protein complexes from dividing cells expressing a tagged but functional version of CDK11. We would also like to study the Drosophila CDK11 homologue. Preliminary work on a P element line inserted in the CDK11 gene suggests that mutation in CDK11 leads to mitotic defects in this organism. Unlike human cells, studying CDK11 in fly will permit to analyse the function of this gene in a developmental context and in different genetic backgrounds. In addition, we will develop transgenic flies with tags (GFP, Myc) to image Fluorescent version of CDK11. CDK11 complexes from mitotic embryos will also be isolated and identified from mitotic embryos. Using both systems, the identification of CDK11 candidate interacting proteins will be validated in vivo and in vitro.

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