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dc.contributor.authorXia, Fang
dc.contributor.authorCanovas, Pedro
dc.contributor.authorGuadagno, Thomas M.
dc.contributor.authorAltieri, Dario C.
dc.date2022-08-11T08:09:38.000
dc.date.accessioned2022-08-23T16:38:30Z
dc.date.available2022-08-23T16:38:30Z
dc.date.issued2008-07-02
dc.date.submitted2009-11-27
dc.identifier.citationMol Cell Biol. 2008 Sep;28(17):5299-311. Epub 2008 Jun 30. <a href="http://dx.doi.org/10.1128/MCB.02039-07">Link to article on publisher's site</a>
dc.identifier.issn1098-5549 (Electronic)
dc.identifier.doi10.1128/MCB.02039-07
dc.identifier.pmid18591255
dc.identifier.urihttp://hdl.handle.net/20.500.14038/39262
dc.description.abstractAberrant 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18591255&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectAnimals
dc.subjectBinding Sites
dc.subjectCell Cycle
dc.subjectCell Cycle Proteins
dc.subjectFibroblasts
dc.subjectGuanosine Triphosphate
dc.subjectHela Cells
dc.subjectHumans
dc.subjectMice
dc.subjectMicrotubule-Associated Proteins
dc.subjectMicrotubules
dc.subjectMitotic Spindle Apparatus
dc.subjectNIH 3T3 Cells
dc.subjectNeoplasm Proteins
dc.subjectNeoplasms
dc.subjectNuclear Proteins
dc.subjectNucleotides
dc.subjectOvum
dc.subjectProtein Binding
dc.subjectProteomics
dc.subjectXenopus
dc.subjectran GTP-Binding Protein
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleA survivin-ran complex regulates spindle formation in tumor cells
dc.typeJournal Article
dc.source.journaltitleMolecular and cellular biology
dc.source.volume28
dc.source.issue17
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=3063&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/2064
dc.identifier.contextkey1073596
refterms.dateFOA2022-08-23T16:38:30Z
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/2064
dc.contributor.departmentDepartment of Cancer Biology
dc.source.pages5299-311


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