Romano Alper, Guse Annika, Krascenicova Ivica, Schnabel Heinke, Schnabel Ralf, Glotzer Michael
Research Institute of Molecular Pathology, Dr. Bohrgasse 7, Vienna A-1030, Austria.
J Cell Biol. 2003 Apr 28;161(2):229-36. doi: 10.1083/jcb.200207117. Epub 2003 Apr 21.
The Aurora B kinase complex is a critical regulator of chromosome segregation and cytokinesis. In Caenorhabditis elegans, AIR-2 (Aurora B) function requires ICP-1 (Incenp) and BIR-1 (Survivin). In various systems, Aurora B binds to orthologues of these proteins. Through genetic analysis, we have identified a new subunit of the Aurora B kinase complex, CSC-1. C. elegans embryos depleted of CSC-1, AIR-2, ICP-1, or BIR-1 have identical phenotypes. CSC-1, BIR-1, and ICP-1 are interdependent for their localization, and all are required for AIR-2 localization. In vitro, CSC-1 binds directly to BIR-1. The CSC-1/BIR-1 complex, but not the individual subunits, associates with ICP-1. CSC-1 associates with ICP-1, BIR-1, and AIR-2 in vivo. ICP-1 dramatically stimulates AIR-2 kinase activity. This activity is not stimulated by CSC-1/BIR-1, suggesting that these two subunits function as targeting subunits for AIR-2 kinase.
极光B激酶复合体是染色体分离和胞质分裂的关键调节因子。在秀丽隐杆线虫中,AIR-2(极光B)的功能需要ICP-1(Incenp)和BIR-1(生存素)。在各种系统中,极光B与这些蛋白质的直系同源物结合。通过遗传分析,我们鉴定出了极光B激酶复合体的一个新亚基CSC-1。缺乏CSC-1、AIR-2、ICP-1或BIR-1的秀丽隐杆线虫胚胎具有相同的表型。CSC-1、BIR-1和ICP-1的定位相互依赖,且所有这些对于AIR-2的定位都是必需的。在体外,CSC-1直接与BIR-1结合。CSC-1/BIR-1复合体而非单个亚基与ICP-1结合。CSC-1在体内与ICP-1、BIR-1和AIR-2结合。ICP-1显著刺激AIR-2激酶活性。CSC-1/BIR-1不刺激这种活性,这表明这两个亚基作为AIR-2激酶的靶向亚基发挥作用。