XCS-1, a maternally expressed gene product involved in regulating mitosis in Xenopus

The regulation of the cell cycle during early development is an important a nd complex biological process. We have cloned a cDNA, XCS-1, that may play an important role in regulating mitosis during early embryogenesis in Xenop us laevis. XCS-1 is a maternally expressed gene product that is the Xenopus homologue of the human cleavage signal protein (CS-1), XCS-1 transcripts w ere detected in oocytes with the titer decreasing just prior to the MET. Du ring development the XCS-1 protein was detected on the membrane and in the nucleus of blastomeres, It was also detected on the mitotic spindle In mito tic cells and on the centrosomes In interphase cells. Overexpression of myc -XCS-1 in Xenopus embryos resulted in abnormal mitoses with increased numbe rs of centrosomes, multipolar spindles, and abnormal distribution of chromo somes. Also, we observed incomplete cytokinesis resulting in multiple nucle i residing in the same cytoplasm with the daughter nuclei in different phas es of the cell cycle. The phenotype depended on the presence of the N termi nus of XCS-1 (aa 1-73) and a consensus NIMA kinase phosphorylation site (aa 159-167). Mutations in this site affected the ability of the overexpressed XCS-1 protein to produce the phenotype. These results suggest that XCS-1 is a maternal factor playing an important role in the regulation of the cell cycle during early embryogenesis and that its function depends on its state of phosphorylation.