The Conserved Kinases CDK-1, GSK-3, KIN-19, and MBK-2 Promote OMA-1 Destruction to Regulate the Oocyte-to-Embryo Transition in C. elegans.
BACKGROUND
At the onset of embryogenesis, key developmental regulators called determinants are activated asymmetrically to specify the body axes and tissue layers. In C. elegans, this process is regulated in part by a conserved family of CCCH-type zinc finger proteins that specify the fates of early embryonic cells. The asymmetric localization of these and other determinants is regulated in early embryos through motor-dependent physical translocation as well as selective proteolysis.


RESULTS
We show here that the CCCH-type zinc finger protein OMA-1 serves as a nexus for signals that regulate the transition from oogenesis to embryogenesis. While OMA-1 promotes oocyte maturation during meiosis, destruction of OMA-1 is needed during the first cell division for the initiation of ZIF-1-dependent proteolysis of cell-fate determinants. Mutations in four conserved protein kinase genes-mbk-2/Dyrk, kin-19/CK1alpha, gsk-3, and cdk-1/CDC2-cause stabilization of OMA-1 protein, and their phenotypes are partially suppressed by an oma-1 loss-of-function mutation. OMA-1 proteolysis also depends on Cyclin B3 and on a ZIF-1-independent CUL-2-based E3 ubiquitin ligase complex, as well as the CUL-2-interacting protein ZYG-11 and the Skp1-related proteins SKR-1 and SKR-2.


CONCLUSIONS
Our findings suggest that a CDK1/Cyclin B3-dependent activity links OMA-1 proteolysis to completion of the first cell cycle and support a model in which OMA-1 functions to prevent the premature activation of cell-fate determinants until after they are asymmetrically partitioned during the first mitosis.
Shirayama
Masaki
M
Program in Molecular Medicine, University of Massachusetts Medical School, 373 Plantation Street, Worcester, Massachusetts 01605.
Soto
Martha C
MC
Ishidate
Takao
T
Kim
Soyoung
S
Nakamura
Kuniaki
K
Bei
Yanxia
Y
van den Heuvel
Sander
S
Mello
Craig C
CC
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D017124:Conserved Sequence; D004625:Embryo, Nonmammalian / Q000166:cytology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C508383:Cks-1 protein, C elegans; D009687:Nuclear Proteins; C440205:OMA-1 protein, C elegans; D051153:Wnt Proteins; C476529:ZIF-1 protein, C elegans; C100950:pie-1 protein, C elegans; D011494:Protein Kinases; C478059:MBK-2 protein, C elegans; D011505:Protein-Tyrosine Kinases; C508382:KIN-19 protein, C elegans; D016203:CDC2 Protein Kinase; D038362:Glycogen Synthase Kinase 3