HOMEODOMAIN-INTERACTING PROTEIN-KINASES, A NOVEL FAMILY OF CO-REPRESSORS FOR HOMEODOMAIN TRANSCRIPTION FACTORS

A novel family of cofactors that differentially interact with homeopro teins have been identified via a yeast two-hybrid screen. The proteins contain a conserved protein kinase domain that is separated from a do main that interacts with homeoproteins and hence are termed homeodomai n-interacting protein kinases (HIPKs): HIPK1, HIPK2, and HIPK3, We sho w that HIPKs are nuclear kinases using GFP-HIPK fusion constructs. The DNA binding activity of the NK-3 homeoprotein is greatly enhanced by HIPK2, but this effect is independent of its phosphorylation by HIPK2. In cultured cells, HIPKs localize to nuclear speckles and potentiate the repressor activities of NK homeoproteins. The co-repressor activit y of HIPKs depends on both its homeodomain interaction domain and a co -repressor domain that maps to the N terminus. Thus, HIPKs represent a heretofore undescribed family of co-repressors for homeodomain transc ription factors.