Research programme 02
DREAM assembly, DYRK1A and the cell-cycle switch
We define the biochemical decisions that assemble repressive DREAM or redirect the MuvB core toward B-MYB–FOXM1 activation.
Central question
Which phosphorylation, protein-interaction and dosage-sensitive mechanisms determine whether MuvB represses or activates cell-cycle genes?
The MuvB core is a molecular switch. In quiescence it joins p130, E2F4 and DP to form DREAM; during cell-cycle re-entry it exchanges those partners for B-MYB and FOXM1, activating genes required for late cell-cycle progression. The laboratory studies the structural and regulatory mechanisms that govern this transition.
A major focus is DYRK1A, a dosage-sensitive kinase encoded on chromosome 21. DYRK1A phosphorylation of LIN52 is required for stable DREAM assembly, linking kinase activity to quiescence, senescence, DNA repair and developmental biology. Current collaborative work examines how DYRK1A dosage and interaction networks shape both normal development and cancer-relevant cell states.
Approaches
- Affinity purification and immunoblotting
- Mass spectrometry and phosphoproteomics
- Protein-structure-guided mutagenesis
- Kinase perturbation
- Proteomic interaction mapping
- Developmental model systems
Selected work
- Insights from the protein interaction Universe of the multifunctional “Goldilocks” kinase DYRK1A (2023)
- DYRK1A protein kinase promotes quiescence and senescence through DREAM complex assembly (2011)
- Evolutionarily conserved multisubunit RBL2/p130 and E2F4 protein complex represses human cell cycle-dependent genes in quiescence (2007)