Identification and functional analyses of cellular proteins that specifically interact with DYRK family protein kinases

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DYRK1A is encoded in the Down's syndrome critical region on human chromosome 21, and plays an important role in the functional regulation of cells. We have identified WDR68, an evolutionarily conserved WD40 protein, as a cellular binding partner of DYRK1A. We showed that WDR68 is indispensable for the optimal proliferation and survival of mammalian cultured cells. DYRK1A and DYRK1B, but not DYRK2, DYRK3, or DYRK4, bound to WDR68. WDR68 was distributed throughout the cell, whereas nuclear accumulation of WDR68 was observed upon co-expression of DYRK1A. Taken together, these results suggest that DYRK1A binds specifically to WDR68 in cells, thereby inducing nuclear translocation of WDR68.