Title |
A small-molecule inhibitor of Haspin alters the kinetochore functions of Aurora B
|
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Published in |
Journal of Cell Biology, October 2012
|
DOI | 10.1083/jcb.201205119 |
Pubmed ID | |
Authors |
Anna De Antoni, Stefano Maffini, Stefan Knapp, Andrea Musacchio, Stefano Santaguida |
Abstract |
By phosphorylating Thr3 of histone H3, Haspin promotes centromeric recruitment of the chromosome passenger complex (CPC) during mitosis. Aurora B kinase, a CPC subunit, sustains chromosome bi-orientation and the spindle assembly checkpoint (SAC). Here, we characterize the small molecule 5-iodotubercidin (5-ITu) as a potent Haspin inhibitor. In vitro, 5-ITu potently inhibited Haspin but not Aurora B. Consistently, 5-ITu counteracted the centromeric localization of the CPC without affecting the bulk of Aurora B activity in HeLa cells. Mislocalization of Aurora B correlated with dephosphorylation of CENP-A and Hec1 and SAC override at high nocodazole concentrations. 5-ITu also impaired kinetochore recruitment of Bub1 and BubR1 kinases, and this effect was reversed by concomitant inhibition of phosphatase activity. Forcing localization of Aurora B to centromeres in 5-ITu also restored Bub1 and BubR1 localization but failed to rescue the SAC override. This result suggests that a target of 5-ITu, possibly Haspin itself, may further contribute to SAC signaling downstream of Aurora B. |
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Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
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Science communicators (journalists, bloggers, editors) | 2 | 67% |
Members of the public | 1 | 33% |
Mendeley readers
Geographical breakdown
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United Kingdom | 2 | 1% |
Netherlands | 1 | <1% |
Korea, Republic of | 1 | <1% |
Japan | 1 | <1% |
United States | 1 | <1% |
Unknown | 129 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
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Researcher | 27 | 20% |
Student > Master | 15 | 11% |
Student > Bachelor | 8 | 6% |
Professor | 6 | 4% |
Other | 19 | 14% |
Unknown | 24 | 18% |
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Medicine and Dentistry | 5 | 4% |
Chemistry | 5 | 4% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 1% |
Other | 6 | 4% |
Unknown | 24 | 18% |