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Updated: May 7, 2026

Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
Published on: September 17, 2012
Specific activation of cdc25 tyrosine phosphatases by B-type cyclins: evidence for multiple roles of mitotic cyclins
1Howard Hughes Medical Institute, Cold Spring Harbor Laboratory, New York 11724.
Abstract:
Two previously unidentified human cdc25 genes have been isolated, cdc25A and cdc25B. Both genes rescue a cdc25ts mutant of fission yeast. Microinjection of anti-cdc25A antibodies into HeLa cells causes their arrest in mitosis. cdc25A and cdc25B display endogenous tyrosine phosphatase activity that is stimulated several-fold, in the absence of cdc2, by stoichiometric addition of either cyclin B1 or B2 but not A or D1. Association between cdc25A and cyclin B1/cdc2 was detected in the HeLa cells. These findings indicate that B-type cyclins are multifunctional proteins that not only act as M phase regulatory subunits of the cdc2 protein kinase, but also activate the cdc25 tyrosine phosphatase, of which cdc2 is the physiological substrate. A region of amino acid similarity between cyclins and tyrosine PTPases has been detected. This region is absent in cdc25 phosphatases. The motif may represent an activating domain that has to be provided to cdc25 by intermolecular interaction with cyclin B.
Insights
Two new human CDC25 genes, cdc25A and cdc25B, were identified. They activate tyrosine phosphatase and are regulated by B-type cyclins, crucial for cell cycle control.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The CDC25 gene product is a key regulator of cell cycle progression.
- Tyrosine phosphorylation plays a critical role in cell cycle control.
Purpose of the Study:
- To identify and characterize novel human CDC25 genes.
- To investigate the regulatory mechanisms of CDC25 tyrosine phosphatase activity.
Main Methods:
- Gene isolation and functional rescue of fission yeast mutants.
- Antibody microinjection into HeLa cells to study mitotic arrest.
- In vitro assays to measure tyrosine phosphatase activity and protein interactions.
Main Results:
- Two novel human CDC25 genes, cdc25A and cdc25B, were isolated and functionally characterized.
- cdc25A and cdc25B exhibit tyrosine phosphatase activity, stimulated by B-type cyclins (B1, B2) but not other cyclin types.
- Association between cdc25A, cyclin B1, and cdc2 was observed in HeLa cells.
- A conserved motif for cyclin interaction was identified in tyrosine phosphatases but absent in cdc25.
Conclusions:
- B-type cyclins are multifunctional, regulating both cdc2 kinase activity and cdc25 tyrosine phosphatase activation.
- cdc25A and cdc25B are key components in the cell cycle control pathway, activated by B-type cyclins.
- Intermolecular interaction with cyclin B likely provides an activating domain to cdc25 phosphatases.
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