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Genes Dev. 1999 May 1;13(9):1067-72.

Binding of 14-3-3 proteins and nuclear export control the intracellular localization of the mitotic inducer Cdc25.

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Division of Biology 216-76, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA.


Binding of 14-3-3 proteins near the nuclear localization sequence of Xenopus Cdc25 suppresses its ability to induce entry into mitosis. We have examined the intracellular localization of green fluorescent protein (GFP)-tagged wild-type Cdc25 or a mutant (S287A) that cannot bind 14-3-3 proteins. Upon coexpression with Myc-14-3-3epsilon, GFP-Cdc25-WT was predominantly cytoplasmic, whereas GFP-Cdc25-S287A was exclusively nuclear. Leptomycin B, an inhibitor of nuclear export, elicited a prompt redistribution of GFP-Cdc25-WT to the nucleus. Mutagenesis experiments demonstrated that Cdc25 contains multiple nuclear export sequences. These studies indicate that the binding of 14-3-3 proteins and nuclear export regulate the intracellular localization of Cdc25.

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