Zeitlin S G, Shelby R D, Sullivan K F
Department of Cell Biology, Scripps Research Institute, La Jolla, CA 92037, USA.
J Cell Biol. 2001 Dec 24;155(7):1147-57. doi: 10.1083/jcb.200108125.
Aurora B is a mitotic protein kinase that phosphorylates histone H3, behaves as a chromosomal passenger protein, and functions in cytokinesis. We investigated a role for Aurora B with respect to human centromere protein A (CENP-A), a centromeric histone H3 homologue. Aurora B concentrates at centromeres in early G2, associates with histone H3 and centromeres at the times when histone H3 and CENP-A are phosphorylated, and phosphorylates histone H3 and CENP-A in vitro at a similar target serine residue. Dominant negative phosphorylation site mutants of CENP-A result in a delay at the terminal stage of cytokinesis (cell separation). The only molecular defects detected in analysis of 22 chromosomal, spindle, and regulatory proteins were disruptions in localization of inner centromere protein (INCENP), Aurora B, and a putative partner phosphatase, PP1gamma1. Our data support a model where CENP-A phosphorylation is involved in regulating Aurora B, INCENP, and PP1gamma1 targeting within the cell. These experiments identify an unexpected role for the kinetochore in regulation of cytokinesis.
极光激酶B是一种有丝分裂蛋白激酶，可使组蛋白H3磷酸化，作为一种染色体乘客蛋白发挥作用，并在胞质分裂中起作用。我们研究了极光激酶B与人类着丝粒蛋白A（CENP - A，一种着丝粒组蛋白H3同源物）相关的作用。极光激酶B在G2早期集中于着丝粒，在组蛋白H3和CENP - A磷酸化时与组蛋白H3和着丝粒结合，并在体外使组蛋白H3和CENP - A在相似的靶丝氨酸残基处磷酸化。CENP - A的显性负性磷酸化位点突变体导致胞质分裂末期（细胞分离）出现延迟。在分析22种染色体、纺锤体和调节蛋白时检测到的唯一分子缺陷是着丝粒内部蛋白（INCENP）、极光激酶B和一种假定的伴侣磷酸酶PP1γ1的定位破坏。我们的数据支持一种模型，即CENP - A磷酸化参与调节细胞内极光激酶B、INCENP和PP1γ1的靶向作用。这些实验确定了动粒在胞质分裂调节中的一个意外作用。
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