The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore–microtubule attachment and in maintaining the spindle assembly checkpoint

By Silke Hauf, R. Cole, S. LaTerra, C. Zimmer, G. Schnapp, Rainer Walter, A. Heckel, Jacques van Meel, C. Rieder, J. Peters. Journal of Cell Biology, 2003

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The proper segregation of sister chromatids in mitosis depends on bipolar attachment of all chromosomes to the mitotic spindle. We have identified the small molecule Hesperadin as an inhibitor of chromosome alignment and segregation. Our data imply that Hesperadin causes this phenotype by inhibiting the function of the mitotic kinase Aurora B. Mammalian cells treated with Hesperadin enter anaphase in the presence of numerous monooriented chromosomes, many of which may have both sister kinetochores attached to one spindle pole (syntelic attachment). Hesperadin also causes cells arrested by taxol or monastrol to enter anaphase within <1 h, whereas cells in nocodazole stay arrested for 3–5 h. Together, our data suggest that Aurora B is required to generate unattached kinetochores on monooriented chromosomes, which in turn could promote bipolar attachment as well as maintain checkpoint signaling.

Subfields: Cell Biology, Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/3a8c0d3f00f6aef329666b06c36e6fed3da582b9

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Citations in the corpus

Shared and separate functions of polo-like kinases and aurora kinases in cancer (2010, background): “gov/drugdictionary/?CdrID=39762">paclitaxel (also known as Taxol)-induced mitotic arres”
Aurora-A — A guardian of poles (2005, background): “Studies have shown that Aurora-B activity is required for the correction of errors that occur when the microtubules attached to the KINETOCHORE during prometaphas”
On the road to cancer: aneuploidy and the mitotic checkpoint (2005, background): “Aurora kinase B activity severs improper microtubule attachments that fail to produce tension between sister centromere”
Non-commercial Research and Educational Use including without Limitation Use in Instruction at Your Institution, Sending It to Specific Colleagues That You Know, and Providing a Copy to Your Institution's Administrator. All Other Uses, Reproduction and Distribution, including without Limitation Comm (2005, neutral): “The angular brackets denote averaging over all internal motions [2,14].”
Aurora-kinase inhibitors as anticancer agents (2004, background): “Several reports have been published describing the first generation of small-molecule inhibitors of Aurora-kinase activit”
Kinetochore microtubule dynamics and attachment stability are regulated by Hec1. (2006, positive): “Partial inhibition of Aurora B kinase activity enhances kMT stability (Hauf et al., 2003; Cimini et al., 2006).”
Genetic disruption of aurora B uncovers an essential role for aurora C during early mammalian development (2011, methodology): “8) (Ditchfield et al., 2003; Hauf et al., 2003), this kinase might partially contribute, possibly as a separate arm (Morrow et al., 2005), to the SAC response by recruiting BubR1 to unattached kinetochores.”
Roles of Aurora Kinases in Mitosis and Tumorigenesis (2007, background): “Although it is not clear whether Hesperadin would cause tumor cell death, ZM447439 has shown its ability.”