Molecular analysis of survivin isoforms: evidence that alternatively spliced variants do not play a role in mitosis

Noton, Elizabeth A, Colnaghi, Rita, Tate, Sharon, Starck, Carlene, Carvalho, Ana, Ferrigno, Paul Ko and Wheatley, Sally P (2006) Molecular analysis of survivin isoforms: evidence that alternatively spliced variants do not play a role in mitosis. Journal of Biological Chemistry, 281 (2). pp. 1286-1295. ISSN 0021-9258

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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-2N2 and survivin-N4Ex3 can interact with wild type survivin but have reduced affinity for survivin s partner protein, borealin, and thus do not localise with the chromosomal passenger complex in vivo. Furthermore, we demonstrate that over-expression of survivin-2N2-GFP or survivin-N4Ex3-GFP does not impede cell cycle progression. We also report that wild type survivin, but not survivin-2N2-GFP or survivin-N4Ex3-GFP, can rescue cell proliferation inhibited by siRNA 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.

Item Type: Article
Additional Information: SPW directed this research and was the corresponding author. This paper was the first to demonstrate that only one form of survivin is required for its role in mitosis, and that two other known isoforms, which are present in some cancer cells, are irrelevant for cell proliferation.
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Rita Colnaghi
Date Deposited: 06 Feb 2012 20:15
Last Modified: 30 Nov 2012 17:06
URI: http://sro.sussex.ac.uk/id/eprint/25011
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