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J. Biol. Chem., Vol. 283, Issue 6, 3289-3296, February 8, 2008

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Nuclear Survivin Has Reduced Stability and Is Not Cytoprotective^*

From the Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RQ, United Kingdom

Survivin is an essential mitotic protein that is overexpressed in many cancers, and its presence is correlated with increased resistance to radiation and chemotherapy. Here we demonstrate that sending survivin into the nucleus accelerates its degradation in a cdh1-dependent manner, abolishes the radio resistance normally conferred to cells by its overexpression, and prevents survivin from inhibiting apoptosis without affecting its mitotic localization. Our data suggest that targeting survivin to the nucleus provides an efficient means of eliminating it from the cell and may prove a novel strategy in cancer treatment, particularly in combination with radiotherapy.

Received for publication, May 31, 2007 , and in revised form, December 5, 2007.

^* 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 by a Medical Research Council Ph. D. studentship.

² To whom correspondence should be addressed. Tel.: 01273-873431; Fax: 01273-678121; E-mail: s.p.wheatley{at}sussex.ac.uk.

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