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PMID: 17199039 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly.

Developmental cell ·Vol. 12 ·No. 1 ·2007-01-00 ·Pages 31-43

Kelly AE, Sampath SC, Maniar TA, Woo EM, Chait BT, Funabiki H

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.

MeSH Terms
Animals Antibodies/immunology Aurora Kinases Cell Extracts Centrosome/metabolism Chromosomal Proteins, Non-Histone/immunology,metabolism Chromosomes/metabolism Enzyme Activation Histones/metabolism Microtubules/metabolism Ovum Phosphorylation Protein Binding Protein Serine-Threonine Kinases/metabolism Spindle Apparatus/chemistry,metabolism Stathmin/metabolism Xenopus/metabolism Xenopus Proteins/immunology,metabolism ran GTP-Binding Protein/metabolism
Chemicals
Antibodies CDCA8 protein, Xenopus Cell Extracts Chromosomal Proteins, Non-Histone Histones INCENP protein, Xenopus Stathmin Xenopus Proteins cdca9 protein, Xenopus Aurora Kinases Protein Serine-Threonine Kinases ran GTP-Binding Protein
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Kelly Alexander E
Laboratory of Chromosome and Cell Biology, The Rockefeller University, New York, NY 10021, USA.
Sampath Srinath C
Maniar Tapan A
Woo Eileen M
Chait Brian T
Funabiki Hironori
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Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1534-5807
DOI
10.1016/j.devcel.2006.11.001
Published
2007-01-00
Pages
31-43
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC1892535
Subset
IM
Grants
NIGMS NIH HHS · GM07739 · United States
NCRR NIH HHS · P41 RR000862 · United States
NIGMS NIH HHS · GM075249 · United States
NCI NIH HHS · CA09673 · United States
NCI NIH HHS · T32 CA009673 · United States
NCRR NIH HHS · RR00862 · United States
NIGMS NIH HHS · T32 GM007739 · United States
NIGMS NIH HHS · R01 GM075249 · United States
External Links
PubMed source DOI: 10.1016/j.devcel.2006.11.001 PMC Full Text View journal details
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