Global Phosphoproteomics of DYRK1A Inhibition in Glioblastoma Cells

Here we performed a detailed investigation to delineate the role of DYRK1A in glioblastoma, using both pharmacological and genetic tools combined with global phosphoproteomics. Our data show that DYRK1A inhibitors affect a much broader proportion of the phosphoproteome than DYRK1A knockdown. By overlaying these datasets we identify a pool of 61 putative novel DYRK1A targets, and validate CDC23 Ser588 as a bona-fide DYRK1A substrate. CDC23 is a ubiquitin ligase that degrades mitotic proteins, and DYRK1A inhibiton thereby leads to the accumulation of cyclin B and activation of CDK1.