Cdc25A localisation and shuttling: characterisation of sequences mediating nuclear export and import

The Cdc25 phosphatases play crucial roles in cell cycle progression by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases. Cdc25A is an important regulator of the G1/S transition but functions also in the mitotic phase of the human cell cycle. In this pap...

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Bibliographic Details
Published in:Experimental cell research 2005-02, Vol.303 (1), p.89-100
Main Authors: Källström, Helena, Lindqvist, Arne, Pospisil, Vitek, Lundgren, Andreas, Karlsson Rosenthal, Christina
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Active Transport, Cell Nucleus - physiology
Amino Acid Sequence
Cdc25
cdc25 Phosphatase/metabolism
cdc25 Phosphatases - metabolism
CELL CYCLE
Cell Nucleus - metabolism
CYTOPLASM
Cytoplasm - metabolism
Exportin 1 Protein
FIBROBLASTS
FLUORESCENCE
HELA CELLS
Humans
Karyopherins - metabolism
Localisation
Medicin och hälsovetenskap
Molecular Sequence Data
Nuclear export sequence (NES)
Nuclear localisation signal (NLS)
Nuclear Localization Signals - metabolism
PHOSPHATASES
PHOSPHOTRANSFERASES
RABBIT TUBES
Receptors, Cytoplasmic and Nuclear - metabolism
Shuttling
THREONINE
TYROSINE
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Summary:The Cdc25 phosphatases play crucial roles in cell cycle progression by removing inhibitory phosphates from tyrosine and threonine residues of cyclin-dependent kinases. Cdc25A is an important regulator of the G1/S transition but functions also in the mitotic phase of the human cell cycle. In this paper, we investigate the sub-cellular localisation of exogenously expressed Cdc25A. We show that YFP-Cdc25A is localised both in the nucleus and the cytoplasm of HeLa cells and untransformed fibroblasts. Cell fusion assays and fluorescence loss in photobleaching (FLIP) assays reveal that the localisation is dynamic and the protein shuttles between the nucleus and the cytoplasm. We demonstrate that nuclear export of Cdc25A is partly mediated by an N-terminal nuclear export sequence (NES), in a manner not sensitive to the Exportin 1-inhibitor leptomycin B. A nuclear localisation signal (NLS) is also characterised, mutation of which leads to cytoplasmic localisation of Cdc25A. Our results imply that the Cdc25A phosphatase may interact with substrates and regulators both in the nucleus and the cytoplasm.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2004.09.012