Signalling by human serine-threonine kinases in cancer biology, neurodegeneration and DNA damage responses

The increased complexity of organisms in evolution requires new layers of regulatory mechanisms. We have identified a human chromatin kinase, VRK1 that plays a complex regulatory role in human biology, and have become the reference group. VRK1 forms complexes with transcription factors such as p53, Sox2, CREB or ATF2 regulating gene transcription, and is critical for entry in cell cycle and proliferation. In cancer, VRK1 is a driver gene associated with poorer prognosis. VRK1 regulates histones chromatin remodeling and its associated epigenetic marks. VRK1 participates in chromatin remodeling in DNA damage, being required for DNA protection (γH2AX) or specific repairs pathways (NBS1, 53BP1). VRK1 also regulates nuclear protein complexes involved in RNA processing, such as Cajal bodies. We try to understand the mechanisms by which alteration of DNA repair leads to neurodegenerative damage. VRK1 mutants are linked to ALS, SMA, ataxia and pontocerebellar hypoplasia.