Innovative identification of atypical CDK-cyclin complexes

The cell cycle is the multi-step process a cell undergoes to divide and make two new cells. Normally, the cell cycle is tightly regulated. Cancer cells however overcome control mechanisms, divide too quickly and keep growing when they shouldnt, forming tumors. The cell cycle is controlled by proteins that directly interact with each other to form complexes, specifically cyclin-dependent kinases (CDKs), their regulatory partners called cyclins, and CDK inhibitors (CKIs). While the basic steps of the cell cycle are understood, recent research shows that CDK complexes are more flexible and interconnected than previously thought, especially in fast- growing cancer cells with abnormal levels of cell cycle regulators. New studies suggest that CDK-cyclin and CDK-cyclin-CKI complexes can form in unexpected compositions, challenging traditional views of how CDKs work. These novel complexes may help cancer cells bypass normal cell cycle control and resist CDK inhibitors used in treatments. However, detecting these complexes is difficult because current methods rely on samples that contain a mix of cells in different cell cycle phases and just one protein of interest with its interaction partners can be analysed. This makes it difficult to find forms that only appear at specific stages. To better understand these complexes, we need detailed studies of CDK interactions during different phases of the cell cycle. We aim to establish a new method to analyse protein-protein interactions in single cells and uncover strategies of cancer cells to manipulate their cell cycle and thereby their division.

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