title: Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly.
abstract: Chromatin-induced spindle assembly depends on regulation of microtubule-depolymerizing proteins by the chromosomal passenger complex (CPC), consisting of Incenp, Survivin, Dasra (Borealin), and the kinase Aurora B, but the mechanism and significance of the spatial regulation of Aurora B activity remain unclear. Here, we show that the Aurora B pathway is suppressed in the cytoplasm of Xenopus egg extract by phosphatases, but that it becomes activated by chromatin via a Ran-independent mechanism. While spindle microtubule assembly normally requires Dasra-dependent chromatin binding of the CPC, this function of Dasra can be bypassed by clustering Aurora B-Incenp by using anti-Incenp antibodies, which stimulate autoactivation among bound complexes. However, such chromatin-independent Aurora B pathway activation promotes centrosomal microtubule assembly and produces aberrant achromosomal spindle-like structures. We propose that chromosomal enrichment of the CPC results in local kinase autoactivation, a mechanism that contributes to the spatial regulation of spindle assembly and possibly to other mitotic processes.
authors.affiliation: Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10021, USA.
authors.forename: Alexander E
authors.initials: AE
authors.lastname: Kelly
authors.forename: Srinath C
authors.initials: SC
authors.lastname: Sampath
authors.forename: Tapan A
authors.initials: TA
authors.lastname: Maniar
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Woo
authors.forename: Brian T
authors.initials: BT
authors.lastname: Chait
authors.forename: Hironori
authors.initials: H
authors.lastname: Funabiki
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D064127:Aurora Kinases; D002457:Cell Extracts; D018385:Centrosome / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000276:immunology / Q000378:metabolism; D002875:Chromosomes / Q000378:metabolism*; D004789:Enzyme Activation; D006657:Histones / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D010063:Ovum; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D008941:Spindle Apparatus / Q000737:chemistry / Q000378:metabolism*; D050777:Stathmin / Q000378:metabolism; D014981:Xenopus / Q000378:metabolism*; D029867:Xenopus Proteins / Q000276:immunology / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000378:metabolism
chemical_list: D000906:Antibodies; C488975:CDCA8 protein, Xenopus; D002457:Cell Extracts; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; C506222:INCENP protein, Xenopus; D050777:Stathmin; D029867:Xenopus Proteins; C488974:cdca9 protein, Xenopus; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D020931:ran GTP-Binding Protein