title: Survivin 2alpha: a novel Survivin splice variant expressed in human malignancies.
abstract: BACKGROUND
  Survivin and its alternative splice forms are involved in critical cellular processes, including cell division and programmed cell death. Survivin is expressed in the majority of human cancers, but minimally in differentiated normal tissues. Expression levels correlate with tumor aggressiveness and resistance to therapy.
  
  
  RESULTS
  In the present study, we identify and characterize a novel survivin isoform that we designate survivin 2alpha. Structurally, the transcript consists of 2 exons: exon 1 and exon 2, as well as a 3' 197 bp region of intron 2. Acquisition of a new in-frame stop codon within intron 2 results in an open reading frame of 225 nucleotides, predicting a truncated 74 amino acid protein. Survivin 2alpha is expressed at high levels in several malignant cell lines and primary tumors. Functional assays show that survivin 2alpha attenuates the anti-apoptotic activity of survivin. Subcellular localization and immunoprecipitation of survivin 2alpha suggests a physical interaction with survivin.
  
  
  CONCLUSIONS
  We characterized a novel survivin splice variant that we designated survivin 2alpha. We hypothesize that survivin 2alpha can alter the anti-apoptotic functions of survivin in malignant cells. Thus survivin 2alpha may be useful as a therapeutic tool in sensitizing chemoresistant tumor cells to chemotherapy.
authors.affiliation: Center for Childhood Cancer, Columbus Children's Research Institute Columbus, OH, USA. caldash@ccri.net <caldash@ccri.net>
authors.forename: Hugo
authors.initials: H
authors.lastname: Caldas
authors.forename: Laura E
authors.initials: LE
authors.lastname: Honsey
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Altura
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D017209:Apoptosis; D001483:Base Sequence; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D040681:Structural Homology, Protein; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D000077022:Survivin
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