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Vol. 13, No. 9, pp. 1067-1072, May 1, 1999
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-14-3-3
, 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.
[Key Words: Cdc2; cell cycle; mitosis; Chk1; phosphorylation]
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