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J. Biol. Chem., Vol. 281, Issue 2, 1286-1295, January 13, 2006

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Molecular Analysis of Survivin Isoforms

EVIDENCE THAT ALTERNATIVELY SPLICED VARIANTS DO NOT PLAY A ROLE IN MITOSIS^*

Elizabeth A. Noton1, Rita Colnaghi2, Sharon Tate23, Carlene Starck, Ana Carvalho¶, Paul Ko Ferrigno4, and Sally P. Wheatley5

From the Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom, the Medical Research Council Cancer Cell Unit, Hutchison/Medical Research Council Research Centre, Hills Road, Cambridge CB2 2XZ, United Kingdom, and the ^¶University of California, San Diego, Ludwig Institute for Cancer Research, La Jolla, California 92093-0660

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-2 and survivin-Ex3 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-2-green fluorescent protein (GFP) or survivin-Ex3-GFP does not impede cell cycle progression. We also report that wild type survivin, but not survivin-2-GFP or survivin-Ex3-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.

Received for publication, August 9, 2005 , and in revised form, November 2, 2005.

^* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ Supported in part by a post-doctoral Human Frontier Science Program Fellowship.

² These authors contributed equally to this work.

³ Holds a Medical Research Council (MRC) studentship.

⁴ Work in the laboratory of P. K. F. was supported by a grant-in-aid to the MRC Cancer Cell Unit.

⁵ A Cancer Research-UK Senior Fellow. To whom correspondence should be addressed. Tel.: 44-1273-873431; Fax: 44-1273-678121; E-mail: s.p.wheatley{at}sussex.ac.uk.

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