Nakamura H, Wu C, Kuang J, Larabell C, Etkin L D
Department of Molecular Genetics and Department of Clinical Investigation, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
J Cell Sci. 2000 Jul;113 ( Pt 13):2497-505. doi: 10.1242/jcs.113.13.2497.
The regulation of the cell cycle during early development is an important and complex biological process. We have cloned a cDNA, XCS-1, that may play an important role in regulating mitosis during early embryogenesis in Xenopus 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 were detected in oocytes with the titer decreasing just prior to the MBT. During 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 mitotic cells and on the centrosomes in interphase cells. Overexpression of myc-XCS-1 in Xenopus embryos resulted in abnormal mitoses with increased numbers of centrosomes, multipolar spindles, and abnormal distribution of chromosomes. Also, we observed incomplete cytokinesis resulting in multiple nuclei residing in the same cytoplasm with the daughter nuclei in different phases of the cell cycle. The phenotype depended on the presence of the N terminus of XCS-1 (aa 1-73) and a consensus NIMA kinase phosphorylation site (aa159-167). 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.
早期发育过程中细胞周期的调控是一个重要且复杂的生物学过程。我们克隆了一个cDNA,即XCS - 1,它可能在非洲爪蟾早期胚胎发育过程中调控有丝分裂方面发挥重要作用。XCS - 1是一种母源表达的基因产物,是人类切割信号蛋白(CS - 1)的非洲爪蟾同源物。在卵母细胞中检测到XCS - 1转录本,其滴度在中囊胚转变(MBT)之前刚好下降。在发育过程中,在卵裂球的膜和细胞核中检测到XCS - 1蛋白。在有丝分裂细胞的有丝分裂纺锤体上以及间期细胞的中心体上也检测到了它。在非洲爪蟾胚胎中过表达myc - XCS - 1会导致有丝分裂异常,中心体数量增加、多极纺锤体以及染色体分布异常。此外,我们观察到胞质分裂不完全,导致多个细胞核存在于同一细胞质中,且子细胞核处于细胞周期的不同阶段。该表型取决于XCS - 1的N末端(第1 - 73位氨基酸)和一个共有NIMA激酶磷酸化位点(第159 - 167位氨基酸)的存在。该位点的突变影响了过表达的XCS - 1蛋白产生该表型的能力。这些结果表明,XCS - 1是一个母源因子,在早期胚胎发育过程中细胞周期调控中发挥重要作用,并且其功能取决于其磷酸化状态。