The Cdc25 family of protein phosphatases positively regulate the cell division
cycle by activating cyclin-dependent protein kinases. In humans and rodents, three
Cdc25 family members denoted Cdc25A, -B, and -C have been identified. The human cdc25c gene encodes a protein with a
predicted molecular mass of 53,000 daltons whose C-terminal domain shares about 37% sequence identity with the
fission yeast cdc25 mitotic inducer. The CDC25 gene product is a protein-tyrosine
phosphatase and human CDC25 protein activates a partially purified
p34(cdc2)/cyclin B complex.
NCBI Summary:
This gene is highly conserved during evolution and it plays a key role in the regulation of cell division. The encoded protein is a tyrosine phosphatase and belongs to the Cdc25 phosphatase family. It directs dephosphorylation of cyclin B-bound CDC2 and triggers entry into mitosis. It is also thought to suppress p53-induced growth arrest. Multiple alternatively spliced transcript variants of this gene have been described, however, the full-length nature of many of them is not known.
Gene whose expression is detected by cDNA array hybridization: oncogenes, tumor
suppressors, cell cycle regulators Rozenn Dalbi?Tran and Pascal Mermilloda
The cell cycle control protein cdc25C is present, and phosphorylated on serine 214 in the transition from germinal vesicle to metaphase II in human oocyte meiosis. Cunat S et al. Cdc25C is a dual specificity phosphatase essential for dephosphorylation and activation of cyclin-dependent kinase 1 (cdk1), a prerequisite step for mitosis in all eucaryotes. Cdc25C activation requires phosphorylation on at least six sites including serine 214 (S214) which is essential for metaphase/anaphase transit. Here, we have investigated S214 phosphorylation during human meiosis with the objectives of determining if this mitotic phosphatase cdc25C participates in final meiotic divisions in human oocytes. One hundred forty-eight human oocytes from controlled ovarian stimulation protocols were stained for immunofluorescence: 33 germinal vesicle (GV), 37 metaphase stage I (MI), and 78 unfertilized metaphase stage II (MII). Results were stage dependent, identical, independent of infertility type, or stimulation protocol. During GV stages, phospho-cdc25C is localized at the oocyte periphery. During early meiosis I (MI), phosphorylated cdc25C is no longer detected until onset of meiosis I. Here, phospho-cdc25C localizes on interstitial microtubules and at the cell periphery corresponding to the point of polar body expulsion. As the first polar body reaches the periphery, phosphorylated cdc25C is localized at the junction corresponding to the mid body position. On polar body expulsion, the interior signal for phospho-cdc25C is lost, but remains clearly visible in the extruded polar body. In atresic or damaged oocytes, the polar body no longer stains for phospho-cdc25C. Human cdc25C is both present and phosphorylated during meiosis I and localizes in a fashion similar to that seen during human mitotic divisions implying that the involvement of cdc25C is conserved and functional in meiotic cells. Mol. Reprod. Dev. (c) 2007 Wiley-Liss, Inc.
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
Unexpected nuclear localization of Cdc25c in bovine oocytes, early embryos and nuclear-transferred embryos. Gall L et al. It is clear from a wide range of studies that the nuclear/cytoplasmic distribution of Cdc25C has important functional consequences for cell cycle control. It is now admitted that in somatic cells, the localization of Cdc25C in the cytoplasm is required to maintain the cell in an interphasic state and that Cdc25C has to translocate to the nucleus just before M-phase to induce mitotic events. We characterized the expression and localization of Cdc25C during oocyte maturation, the first embryo mitosis and the first steps of somatic cell nuclear transfer (SCNT) in cattle. We demonstrated that Cdc25C was expressed throughout the maturation process and the early development. We clearly showed that Cdc25C was localized in the nucleus at the germinal vesicle stage and during the early development until the blastocyst stage. However the signal change in blastocyst and Cdc25C became cytoplamic as is the case in somatic cells. Thus oocytes and early embryonic cells presented a specific nuclear Cdc25C localization different from that one observed in somatic cells, suggesting that Cdc25C could have a particular localization/regulation in undifferentiated cells. Following SCNT, Cdc25C became nuclear as soon as the nucleus swelled, and this localization persisted until the blastocyst stage, as is the case in in vitro fertilized embryos. Cdc25C nuclear localization appeared to constitute a major change, which could be associated with reorganization of the somatic nucleus upon nuclear transfer.
Follicle stages
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: fertile Comment:Chen MS, 2001 et al reported absence of apparent phenotype in mice lacking Cdc25C protein
phosphatase.
Cdc25C(-/-)
mice are viable and do not display any obvious abnormalities. Among adult
tissues in which Cdc25C is detected, its transcripts are most abundant in testis,
followed by thymus, ovary, spleen, and intestine. Mice lacking Cdc25C were
fertile, indicating that Cdc25C does not contribute an essential function during
spermatogenesis or oogenesis in the mouse. T- and B-cell development was also
found to be normal in Cdc25C(-/-) mice, and Cdc25C(-/-) mouse splenic T and B
cells exhibited normal proliferative responses in vitro. Finally, the
phosphorylation status of Cdc2, the timing of entry into mitosis, and the cellular
response to DNA damage were unperturbed in mouse embryo fibroblasts lacking
Cdc25C. These findings indicate that Cdc25A and/or Cdc25B may compensate for
loss of Cdc25C in the mouse.