During mitosis, the chromosomal passenger complex (CPC) comprising the Aurora B kinase, INCENP, survivin and borealin is essential for correcting non-bipolar chromosome attachments and for cytokinesis. In addition, the CPC might fullfil a role in the mitotic spindle assembly checkpoint (SAC), but this activity might be related to its role in correcting non-bipolar chromosome attachments. Here, we demonstrate that treatment of mitotic cells with the antibiotic actinomycin D causes a displacement of an intact and active CPC from centromeres onto chromosome arms, which results in chromosome misalignment, cytokinesis failure and SAC override, but still preserves histone H3 phosphorylation on chromosome arms. This surprising and unique scenario allows the reconstitution of endogenous Aurora B at centromeres/inner kinetochores by expressing a Cenp-B-INCENP fusion protein. We find that although the selective recruitment of endogenous Aurora B to centromeres/inner kinetochores is not sufficient to restore chromosome alignment and cytokinesis, it can restore Cenp-A phosphorylation at kinetochores, BubR1 recruitment to kinetochores and SAC activity after spindle disruption. These results indicate that INCENP-Aurora B localized at centromeres/inner kinetochores is sufficient to mediate SAC activity upon spindle disruption.
详细资料
文献种类: Journal Article
期刊名称: Cell Cycle (Georgetown, Tex.)
期刊缩写: Cell Cycle
期卷页: 2010年第9卷第7期
地址: Philipps University Marburg, Institute for Molecular Biology and Tumor Research (IMT), Marburg, Germany
原来actinomycin D可以让CPC复合物从centromere转位到chromosome arm,虽然机制还不清楚,但是有可能作为工具用到。正如文中所说This surprising and unique scenario allows the reconstitution of endogenous Aurora B at centromeres/inner kinetochores。