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Molecular and Cellular Biology, September 2008, p. 5299-5311, Vol. 28, No. 17
0270-7306/08/$08.00+0     doi:10.1128/MCB.02039-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

A Survivin-Ran Complex Regulates Spindle Formation in Tumor Cells{triangledown}

Fang Xia,1 Pedro M. Canovas,1 Thomas M. Guadagno,2 and Dario C. Altieri1*

Department of Cancer Biology and Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01605,1 Department of Interdisciplinary Oncology, Molecular Oncology Program, H. Lee Moffitt Comprehensive Cancer Center, Tampa, Florida 336122

Received 12 November 2007/ Returned for modification 18 February 2008/ Accepted 19 June 2008

Aberrant cell division is a hallmark of cancer, but the molecular circuitries of this process in tumor cells are not well understood. Here, we used a high-throughput proteomics screening to identify novel molecular partners of survivin, an essential regulator of mitosis overexpressed in cancer. We found that survivin associates with the small GTPase Ran in an evolutionarily conserved recognition in mammalian cells and Xenopus laevis extracts. This interaction is regulated during the cell cycle, involves Ran-GTP, requires a discrete binding interface centered on Glu65 in survivin, and is independent of the Ran effector Crm1. Disruption of a survivin-Ran complex does not affect the assembly of survivin within the chromosomal passenger complex or its cytosolic accumulation, but it inhibits the delivery of the Ran effector molecule TPX2 to microtubules. In turn, this results in aberrant mitotic spindle formation and chromosome missegregation in tumor, but not normal, cells. Therefore, survivin is a novel effector of Ran signaling, and this pathway may be preferentially exploited for spindle assembly in tumor cells.

* Corresponding author. Mailing address: Department of Cancer Biology, LRB428, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA 01605. Phone: (508) 856-5775. Fax: (508) 856-5792. E-mail: dario.altieri{at}umassmed.edu

{triangledown} Published ahead of print on 30 June 2008.

Molecular and Cellular Biology, September 2008, p. 5299-5311, Vol. 28, No. 17
0270-7306/08/$08.00+0     doi:10.1128/MCB.02039-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Xia, F., Lee, C. W., Altieri, D. C. (2009). Comment re: Ran-GTP Control of Tumor Cell Mitosis. Cancer Res. 69: 1240-1241 [Full Text]  


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