dc.contributor.author | Santaguida, Stefano | |
dc.contributor.author | De Antoni, Anna | |
dc.contributor.author | Maffini, Stefano | |
dc.contributor.author | Knapp, Stefan | |
dc.contributor.author | Musacchio, Andrea | |
dc.date.accessioned | 2013-03-12T19:07:50Z | |
dc.date.available | 2013-03-12T19:07:50Z | |
dc.date.issued | 2012-10 | |
dc.date.submitted | 2012-09 | |
dc.identifier.issn | 0021-9525 | |
dc.identifier.issn | 1540-8140 | |
dc.identifier.uri | http://hdl.handle.net/1721.1/77635 | |
dc.description.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. | en_US |
dc.language.iso | en_US | |
dc.publisher | Rockefeller University Press | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1083/jcb.201205119 | en_US |
dc.rights | Creative Commons Attribution 3.0 | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/ | en_US |
dc.source | Rockefeller UP | en_US |
dc.title | A small-molecule inhibitor of Haspin alters the kinetochore functions of Aurora B | en_US |
dc.type | Article | en_US |
dc.identifier.citation | De Antoni, A. et al. “A Small-molecule Inhibitor of Haspin Alters the Kinetochore Functions of Aurora B.” The Journal of Cell Biology 199.2 (2012): 269–284. | en_US |
dc.contributor.department | Koch Institute for Integrative Cancer Research at MIT | en_US |
dc.contributor.mitauthor | Santaguida, Stefano | |
dc.relation.journal | Journal of Cell Biology | en_US |
dc.eprint.version | Final published version | en_US |
dc.type.uri | http://purl.org/eprint/type/JournalArticle | en_US |
eprint.status | http://purl.org/eprint/status/PeerReviewed | en_US |
dspace.orderedauthors | De Antoni, A.; Maffini, S.; Knapp, S.; Musacchio, A.; Santaguida, S. | en |
dc.identifier.orcid | https://orcid.org/0000-0002-1501-6190 | |
mit.license | PUBLISHER_CC | en_US |
mit.metadata.status | Complete | |