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- Title
Subcellular localisation of Cdc25A determines cell fate.
- Authors
Leisser, C.; Rosenberger, G.; Maier, S.; Fuhrmann, G.; Grusch, M.; Strasser, S.; Huettenbrenner, S.; Fassl, S.; Polgar, D.; Krieger, S.; Cerni, C.; Hofer-Warbinek, R.; deMartin, R.; Krupitza, G.
- Abstract
Cell division cycle 25A (Cdc25A) was shown to colocalise both with nuclear and cytoplasmic proteins. Recently, we have demonstrated that overexpressed Cdc25A promoted the survival of rat 423 cells through indirect activation of PKB-protein kinase B. Using a Cdc25A:ER fusion protein, which can be shuttled from the cytoplasm into the nucleus, the present investigation evidences that the antiapoptotic effect of Cdc25A was restricted to its cytoplasmic localisation in rat 423 cells. In contrast, nuclear Cdc25A overexpression caused dephosphorylation and nuclear retention of the proapoptotic transcription factor Forkhead in rhabdomyosarcoma-like 1 (FKHRL1) in human N.1 ovarian carcinoma cells. This resulted in the increased constitutive expression of the FKHRL1 targets Fas ligand and Bim, and promoted apoptosis. Thus, the Cdc25A oncogene, which was found to be frequently overexpressed in certain human cancers, can increase or decrease the susceptibility to apoptosis depending on the cell-type-specific subcellular distribution.Cell Death and Differentiation (2004) 11, 80-89. doi:10.1038/sj.cdd.4401318 Published online 5 September 2003
- Subjects
CELL division; APOPTOSIS; CYTOPLASM; OVARIAN cancer; TRANSCRIPTION factors; CANCER cells
- Publication
Cell Death & Differentiation, 2004, Vol 11, Issue 1, p80
- ISSN
1350-9047
- Publication type
Article
- DOI
10.1038/sj.cdd.4401318