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Nuclear export is essential for the tumor‐promoting activity of survivin
Author(s) -
Knauer Shirley K.,
Krämer Oliver H.,
Knösel Thomas,
Engels Knut,
Rödel Franz,
Kovács Adorján F.,
Dietmaier Wolfgang,
KleinHitpass Ludger,
Habtemichael Negusse,
Schweitzer Andrea,
Brieger Jürgen,
Rödel Claus,
Mann Wolf,
Petersen Iver,
Heinzel Thorsten,
Stauber Roland H.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-5741com
Subject(s) - survivin , nuclear export signal , cancer research , carcinogenesis , mitosis , apoptosis , microbiology and biotechnology , inhibitor of apoptosis , chemistry , nuclear localization sequence , biology , cancer , programmed cell death , cell nucleus , biochemistry , genetics , nucleus
Survivin appears to function as an apoptosis inhibitor and a regulator of cell division during development and tumorigenesis. Here we report the molecular characterization of the nucleocytoplasmic transport of survivin and its potential implications for tumorigenesis. We identified an evolutionary conserved Crm1‐dependent nuclear export signal (NES) in survivin. In dividing cells, the NES is essential for tethering survivin and the survivin/Aurora‐B kinase complex to the mitotic machinery, which in turn appears to be essential for proper cell division. In addition, export seems to be required for the cytoprotective activity of survivin, as export‐deficient survivin fails to protect tumor cells against chemo‐and radiotherapy‐induced apoptosis. These findings appear to be clinically relevant since preferential nuclear localization of survivin correlated with enhanced survival in colorectal cancer patients. Targeting survivin's nuclear export by the application of NES‐specific antibodies promoted its nuclear accumulation and inhibited its cytoprotective function. We demonstrate that nuclear export is essential for the biological activity of survivin and promote the identification of molecular decoys to specifically interfere with survivin's nuclear export as potential anticancer therapeutics. Knauer, S. K., Krämer, O. H., Knösel, T., Engels, K., Rödel, F., Kovács, A. F., Dietmaier, W., Klein‐Hitpass, L., Habtemichael, N., Schweitzer, A., Brieger, J., Rödel, C., Mann, W., Petersen, I., Heinzel, T., Stauber, R. H. Nuclear export is essential for the tumor‐promoting activity of survivin. FASEB J. 21, 207–216 (2007)