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Absence of Cdc25 arrests cells in G2, but still allows activation of the G2-M checkpoint, implicating that both the activation of Wee1 and deactivation of Cdc25 as important regulatory steps in the checkpoint. [11] Inactivation of Chk1 is sufficient to surpass the checkpoint and promote entry into mitosis, regardless if DNA damage is repaired.
Cdc25 is a dual-specificity phosphatase first isolated from the yeast Schizosaccharomyces pombe as a cell cycle defective mutant. [1] As with other cell cycle proteins or genes such as Cdc2 and Cdc4 , the "cdc" in its name refers to " c ell d ivision c ycle". [ 2 ]
An additional function of Plk1 is to activate Cdc25 through phosphorylation. The compound effect of Wee1 degradation and Cdc25 activation is the net removal of inhibitory phosphorylation from cdc2, which activates cdc2. Plk1 is activated at the G2/M transition by the Aurora A and Bora, which accumulate during G2 and form an activation complex.
Chk1 inhibits Cdc25 activity both directly and by promoting its exclusion from the nucleus. [7] The net effect is an increase in the threshold of cyclin B1 required to initiate the hysteretic transition to M-phase, effectively stalling the cell in G2 until the damage is repaired by mechanisms such as homology-directed repair (see above).
In addition, two other residues on the CDK1 subunit must be activated by dephosphorylation. CDC25 removes a phosphate from residues Threonine-14 (Thr-14) and Tyrosine-15 (Tyr-15) and adds a hydroxyl group. Cyclin B/CDK1 activates CDC25 resulting in a positive feedback loop.
The eukaryotic cell cycle consists of four distinct phases: G 1 phase, S phase (synthesis), G 2 phase (collectively known as interphase) and M phase (mitosis and cytokinesis). M phase is itself composed of two tightly coupled processes: mitosis, in which the cell's nucleus divides, and cytokinesis, in which the cell's cytoplasm and cell membrane divides forming two daughter cells.
The CDC25 homology domain, also called the RasGEF domain, is the catalytic domain of many Ras GEFs, which activate Ras GTPases. The CDC25 domain comprises approximately 500 amino acids and was first identified in the CDC25 protein in budding yeast ( Saccharomyces cerevisiae ) .
993 12530 Ensembl ENSG00000164045 ENSMUSG00000032477 UniProt P30304 P48964 RefSeq (mRNA) NM_001789 NM_201567 NM_007658 RefSeq (protein) NP_001780 NP_963861 NP_031684 Location (UCSC) Chr 3: 48.16 – 48.19 Mb Chr 9: 109.7 – 109.72 Mb PubMed search Wikidata View/Edit Human View/Edit Mouse M-phase inducer phosphatase 1 also known as dual specificity phosphatase Cdc25A is a protein that in ...