Cell cycle roles for two 14-3-3 proteins during Drosophila development.
Drosophila 14-3-3 epsilon and 14-3-3 zeta 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 epsilon and 14-3-3 zeta mutants: 14-3-3 epsilon is required to time mitosis in undisturbed post-blastoderm cell cycles and to delay mitosis following irradiation; 14-3-3 zeta 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.
Su
T T
TT
MCD Biology, University of Colorado, Boulder, CO 80309, USA. tin.su@colorado.edu
Parry
D H
DH
Donahoe
B
B
Chien
C T
CT
O'Farrell
P H
PH
Purdy
A
A
D048948:14-3-3 Proteins; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004330:Drosophila / Q000166:cytology* / Q000254:growth & development; D004625:Embryo, Nonmammalian / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008938:Mitosis / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism*
D048948:14-3-3 Proteins; D014446:Tyrosine 3-Monooxygenase; D016203:CDC2 Protein Kinase