Studies on the Role of DIk/ZIP-Kinase in Mitosis and Cytokinesis

DIk/ZIP 激酶在有丝分裂和细胞分裂中作用的研究

• 批准号: 70898914
• 负责人: Professor Dr. Karl Heinz Scheidtmann
• 金额: --
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2008
• 资助国家: 德国
• 起止时间: 2007-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/70898914?language=en
• 关键词: Studies; Role; DIk; ZIP; Kinase

Dlk, or more commonly termed ZIP kinase, plays a key role in regulation of cell motility, contractility, and mitosis, particularly cytokinesis. During mitosis, ZIP kinase associates with centrosomes, centromeres, the contractile ring and the midbody. Recent data revealed by mutant AC2NLS suggest that ZIP kinase plays a role in spindle assembly and in coordination of mitosis and cytokinesis and that these functions involve interaction with centromeres. In the following proposal we want to further elucidate the role of ZIP kinase at centromeres and the significance of centromere-specific H3T11 phosphorylation. We propose that ZIP kinase phosphorylates histone H3 at T11 and that this modification is either part of a centromere-specific histone code or that it is a signal for subsequent incorporation of CENP-A into chromatin. To proof these assumptions we want to 1} express mutant AC2NLS in an inducible fashion and follow its effects under synchronous conditions, 2) identify the interaction partners of ZIP kinase at mitotic structures, 3) establish inducible knockout systems 4) investigate chromosome-directed spindle assembly 5) investigate the role of H3T11 phosphorylation.

Dlk，或更通常称为ZIP激酶，在调节细胞运动性、收缩性和有丝分裂，特别是胞质分裂中起关键作用。在有丝分裂过程中，ZIP激酶与中心体、着丝粒、收缩环和中间体相关联。最近的数据显示突变AC 2NLS的ZIP激酶在纺锤体组装和有丝分裂和胞质分裂的协调中发挥作用，这些功能涉及与着丝粒的相互作用。在下面的建议中，我们希望进一步阐明ZIP激酶在着丝粒中的作用以及着丝粒特异性H3 T11磷酸化的意义。我们提出ZIP激酶磷酸化组蛋白H3在T11，这种修饰要么是一个着丝粒特异性组蛋白代码的一部分，或者它是一个信号，随后纳入CENP-A到染色质。为了证明这些假设，我们想要1）以诱导型方式表达突变体AC 2NLS并在同步条件下跟踪其作用，2）鉴定ZIP激酶在有丝分裂结构处的相互作用配偶体，3）建立诱导型敲除系统，4）研究染色体指导的纺锤体组装，5）研究H3 T11磷酸化的作用。