title: Molecular analysis of survivin isoforms: evidence that alternatively spliced variants do not play a role in mitosis.
abstract: Survivin is a protein with proposed roles in cell division and apoptosis. Transcripts encoding splice variants of human survivin have been described and their expression correlated with cancer progression. As survivin forms homodimers in vitro, it has been suggested that these isoforms could interfere with wild type function by forming heterodimers. Here we show that survivin-2beta and survivin-deltaEx3 can interact with wild type survivin but have reduced affinity for the partner protein of survivin, borealin, and thus do not localize with the chromosomal passenger complex in vivo. Furthermore, we demonstrate that overexpression of survivin-2beta-green fluorescent protein (GFP) or survivin-deltaEx3-GFP does not impede cell cycle progression. We also report that wild type survivin, but not survivin-2beta-GFP or survivin-deltaEx3-GFP, can rescue cell proliferation inhibited by small interfering RNA-mediated survivin depletion. These data suggest that, despite their ability to interact with wild type survivin, neither of these isoforms acts as its competitor during mitosis nor has an essential function.
authors.affiliation: Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Noton
authors.forename: Rita
authors.initials: R
authors.lastname: Colnaghi
authors.forename: Sharon
authors.initials: S
authors.lastname: Tate
authors.forename: Carlene
authors.initials: C
authors.lastname: Starck
authors.forename: Ana
authors.initials: A
authors.lastname: Carvalho
authors.forename: Paul
authors.initials: P
authors.lastname: Ko Ferrigno
authors.forename: Sally P
authors.initials: SP
authors.lastname: Wheatley
mesh_terms: D017398:Alternative Splicing; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry; D045744:Cell Line, Tumor; D002875:Chromosomes / Q000648:ultrastructure; D003001:Cloning, Molecular; D017931:DNA Primers / Q000737:chemistry; D019281:Dimerization; D018450:Disease Progression; D005816:Genetic Complementation Test; D014644:Genetic Variation; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D047468:Immunoprecipitation; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins / Q000737:chemistry*; D008938:Mitosis; D009363:Neoplasm Proteins / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011379:Prognosis; D020033:Protein Isoforms; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D000077022:Survivin; D013997:Time Factors
chemical_list: C107489:BIRC5 protein, human; C490157:CDCA8 protein, human; D018797:Cell Cycle Proteins; D017931:DNA Primers; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010455:Peptides; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D000077022:Survivin; D049452:Green Fluorescent Proteins