Disease relevance of cdc25

• Nine independent primary transformants were regenerated containing the cdc25 sequence under the control of a cauliflower mosaic virus 35S gene promoter [1].

High impact information on cdc25

• Furthermore, mutation of nimT, which encodes a protein with 50% similarity to fission yeast cdc25, causes a G2 arrest and prevents tyrosine dephosphorylation of p34cdc2 but does not prevent full activation of the NIMA protein kinase [2].
• Therefore, the cdc25+, cdc13+, and suc1+ gene products are important for regulating p34cdc2 protein kinase activity during entry into, progress through, and exit from mitosis [3].
• The cell-cycle timing of mitosis in fission yeast is determined by the cdc25+ gene product activating the p34cdc2 protein kinase leading to mitotic initiation [3].
• Activation of the preformed cdc2/cdc13 complex at the G2/M transition requires cdc25+ gene function [4].
• In the fission yeast S. pombe the cdc25+ gene function is required to initiate mitosis [5].

Biological context of cdc25

• Similarly, in fission yeast, the cdc25 and cdc2 gene products influence the ability of cells to delay mitosis in response to the inhibition of DNA synthesis [6].
• Mitotic delay in response to DNA damage is thus distinct from the delay induced by inhibition of DNA synthesis, which involves cdc25 but is not dependent on wee1 [6].
• We have cloned the cdc25+ gene and have found that increased cdc25+ expression causes mitosis to initiate at a reduced cell size [5].
• By indirect immunofluorescence, cdc25 protein is found essentially localized in the nucleus throughout interphase and during early prophase [7].
• During metaphase and anaphase, cdc25 staining remains distributed throughout the cell and excludes the condensed chromosomes [7].

Anatomical context of cdc25

• Just before the complete nuclear envelope breakdown at the prophase-prometaphase boundary, cdc25 proteins are redistributed throughout the cytoplasm [7].
• Using affinity-purified antibodies raised against a synthetic peptide corresponding to the catalytic site of the cdc25 phosphatase, we show that cdc25 protein is constitutively expressed throughout the cell cycle of nontransformed mammalian fibroblasts and does not undergo major changes in protein level [7].
• By engineering fission yeast mutants with diminished eIF4A activity, we have found that translation of cdc25 mRNAs (a dosage-dependent activator of mitosis in all eukaryotic cells) is particularly sensitive to limitations of protein synthesis mediated by limited eIF4A activity [8].
• The cdc25B gene is one of three human cdc25 homologs which can complement the temperature-sensitive cdc25 mutation of Schizosaccharomyces pombe, and is expressed a high levels in human cell lines, particularly in some cancer cells [9].
• Confirming this notion, we find that ectopic expression of the String/cdc25 phosphatase, which is known to activate the cdc2 kinase before mitosis, results in a partial rescue of meiotic divisions in twine mutant testis [10].

Associations of cdc25 with chemical compounds

• Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins [11].
• Mutation of the cdc25 Cys480 codon, corresponding to an essential cysteine in the active site of PTPases, abolished the phosphatase activity of GST-cdc25 [12].
• When challenged with hydroxyurea, stf1-1 acts additively with cdc2-3w in rescuing cdc25 mutants and in allowing mitosis to occur without DNA synthesis [13].
• Expression of fission yeast cdc25 driven by the wheat ADP-glucose pyrophosphorylase large subunit promoter reduces pollen viability and prevents transmission of the transgene in wheat [14].
• Expression of the fission yeast cell cycle regulator cdc25 induces de novo shoot formation in tobacco: evidence of a cytokinin-like effect by this mitotic activator [15].

Regulatory relationships of cdc25

• The presence of a wee1 mutation phenotypically suppresses cdc25 mutations [16].

Other interactions of cdc25

• A family of proteins homologous to the cdc25 gene product of the fission yeast bear specific protein tyrosine phosphatase activity involved in the activation of the p34cdc2-cyclin B kinase [7].
• A lethal interaction of spc1 and cdc25 mutations shows that Spc1 promotes the onset of mitosis [17].
• Disruption of either gene rescues the G2 arrest caused by mutation of the cdc25 mitotic inducer, though the effect of pyp1-disruption is more pronounced [18].
• This fact suggests that in WT the rate-limiting molecular process during the G2 timer is the Tyr15 dephosphorylation of cdc2, for which the cdc25 phosphatase (together with its back-up, pyp3) is dependent [19].
• Similarly, it does not operate through cdc25 since it rescues the disruption. stf1 appears to encode an important new element of mitotic control [20].

References