Survivin 2α:: a novel survivin splice variant expressed in human malignancies

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 2 alpha. 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 2 alpha is expressed at high levels in several malignant cell lines and primary tumors. Functional assays show that survivin 2 alpha attenuates the anti-apoptotic activity of survivin. Subcellular localization and immunoprecipitation of survivin 2 alpha suggests a physical interaction with survivin. Conclusion: We characterized a novel survivin splice variant that we designated survivin 2 alpha. We hypothesize that survivin 2 alpha can alter the anti-apoptotic functions of survivin in malignant cells. Thus survivin 2a may be useful as a therapeutic tool in sensitizing chemoresistant tumor cells to chemotherapy.