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Cell Cycle. 2014;13(14):2248-61. doi: 10.4161/cc.29270. Epub 2014 May 29.

Spatial regulation of Aurora A activity during mitotic spindle assembly requires RHAMM to correctly localize TPX2.

Author information

1
Department of Pediatrics; Child and Family Research Institute; University of British Columbia; Vancouver, British Columbia, Canada.
2
Department of Gynaecology and Obstetrics; University Hospital Düsseldorf; Heinrich-Heine University; Düsseldorf, Germany.
3
Department of Oncology; University of Alberta and Cross Cancer Institute; Edmonton, Alberta, Canada.

Abstract

Construction of a mitotic spindle requires biochemical pathways to assemble spindle microtubules and structural proteins to organize these microtubules into a bipolar array. Through a complex with dynein, the receptor for hyaluronan-mediated motility (RHAMM) cross-links mitotic microtubules to provide structural support, maintain spindle integrity, and correctly orient the mitotic spindle. Here, we locate RHAMM to sites of microtubule assembly at centrosomes and non-centrosome sites near kinetochores and demonstrate that RHAMM is required for the activation of Aurora kinase A. Silencing of RHAMM delays the kinetics of spindle assembly, mislocalizes targeting protein for XKlp2 (TPX2), and attenuates the localized activation of Aurora kinase A with a consequent reduction in mitotic spindle length. The RHAMM-TPX2 complex requires a C-terminal basic leucine zipper in RHAMM and a domain that includes the nuclear localization signal in TPX2. Together, our findings identify RHAMM as a critical regulator for Aurora kinase A signaling and suggest that RHAMM ensures bipolar spindle assembly and mitotic progression through the integration of biochemical and structural pathways.

KEYWORDS:

Aurora kinase A; RHAMM; TPX2; mitosis; spindle assembly

PMID:
24875404
PMCID:
PMC4111680
DOI:
10.4161/cc.29270
[Indexed for MEDLINE]
Free PMC Article

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