A survivin-ran complex regulates spindle formation in tumor cells
UMass Chan Affiliations
Department of Cancer BiologyDocument Type
Journal ArticlePublication Date
2008-07-02Keywords
AnimalsBinding Sites
Cell Cycle
Cell Cycle Proteins
Fibroblasts
Guanosine Triphosphate
Hela Cells
Humans
Mice
Microtubule-Associated Proteins
Microtubules
Mitotic Spindle Apparatus
NIH 3T3 Cells
Neoplasm Proteins
Neoplasms
Nuclear Proteins
Nucleotides
Ovum
Protein Binding
Proteomics
Xenopus
ran GTP-Binding Protein
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
Mol Cell Biol. 2008 Sep;28(17):5299-311. Epub 2008 Jun 30. Link to article on publisher's siteDOI
10.1128/MCB.02039-07Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39262PubMed ID
18591255Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1128/MCB.02039-07
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