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Cell cycle roles for two 14-3-3 proteins during Drosophila development

¹ MCD Biology, University of Colorado, Boulder, CO 80309, USA
² Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA
³ Institute of Molecular Biology, Academia Sinica, Nankang, Taipei, Taiwan

*Author for correspondence (e-mail: tin.su{at}colorado.edu)

Accepted June 10, 2001

Drosophila 14-3-3 and 14-3-3 proteins have been shown to function in RAS/MAP kinase pathways that influence the differentiation of the adult eye and the embryo. Because 14-3-3 proteins have a conserved involvement in cell cycle checkpoints in other systems, we asked (1) whether Drosophila 14-3-3 proteins also function in cell cycle regulation, and (2) whether cell proliferation during Drosophila development has different requirements for the two 14-3-3 proteins. We find that antibody staining for 14-3-3 family members is cytoplasmic in interphase and perichromosomal in mitosis. Using mutants of cyclins, Cdk1 and Cdc25^string to manipulate Cdk1 activity, we found that the localization of 14-3-3 proteins is coupled to Cdk1 activity and cell cycle stage. Relocalization of 14-3-3 proteins with cell cycle progression suggested cell-cycle-specific roles. This notion is confirmed by the phenotypes of 14-3-3 and 14-3-3 mutants: 14-3-3 is required to time mitosis in undisturbed post-blastoderm cell cycles and to delay mitosis following irradiation; 14-3-3 is required for normal chromosome separation during syncytial mitoses. We suggest a model in which 14-3-3 proteins act in the undisturbed cell cycle to set a threshold for entry into mitosis by suppressing Cdk1 activity, to block mitosis following radiation damage and to facilitate proper exit from mitosis.

Key words: Drosophila, Cell Cycle, Checkpoint, Mitosis, 14-3-3

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