DAP-like kinase interacts with the rat homolog of Schizosaccharomyces pombe CDC5 protein, a factor involved in pre-mRNA splicing and required for G_2/M phase transition

摘要

DAP-like kinase (DIK, also termed ZIP kinase) is a leucine zipper-containing serine/threonine-specific protein kinase with as yet unknown biological function(s). Interaction partners so far identified are either transcription factors or proteins that can support or counteract apoptosis. Thus, DIK might be involved in regulating transcription or, more generally, survival or apoptosis. Here we report on a new interaction partner, the rat homolog of Schizosaccharomyces pombe CDC5 protein, a presumptive transcription and splicing factor involved in the G_2/M transition. In vitro, rat CDC5 forms complexes with, but is not phosphorylated by, DIK. Rather, it was phosphorylated by an associated kinase which was identified as CK2. The interaction domain of DIK was mapped to the leucine zipper, while that of CDC5 was mapped to the C-terminal region between residues 500 and 802. In vivo, both proteins co-localize perfectly in distinct speckle-like structures in the nucleus, some of which overlap with promyelocytic leukemia protein. Interestingly, splicing factor SC35, which also resides in speckles, was partially displaced upon overexpression of either CDC5 or DIK, perhaps due to phosphorylation by DIK. Together with previous data, these results suggest that DIK might play a role in coordinating specific transcription and splicing events.