Related Experiment Video
Updated: Jun 1, 2025
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
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Revisiting phosphoregulation of Cdc25C during M-phase induction
Tan Tan1,2, Chuanfen Wu1, Ruoning Wang1
1Department of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Iscience
|January 21, 2025
Summary
M-phase entry involves Cdc25C supershift and activation. Site-comprehensive phosphorylation of Cdc25C
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- Cdc25C phosphatase is crucial for cell cycle progression.
- A positive feedback loop involving Cdk1 and Cdc25C regulates M-phase entry.
- The sudden mobility shift of Cdc25C at M-phase onset is a key regulatory event.
Purpose of the Study:
- To elucidate the molecular mechanisms driving Cdc25C's M-phase supershift and activation.
- To investigate the role of phosphorylation in Cdc25C regulation.
- To differentiate between pre-M-phase and M-phase onset phosphorylation events.
Main Methods:
- Analysis of Cdc25C gel mobility shifts.
- Phosphorylation assays using Cdk1 and other mitotic kinases.
- Investigation of intrinsically disordered protein domains.
- Characterization of phosphorylation machinery assembly and activity.
Main Results:
- Site-comprehensive phosphorylation of Cdc25C's disordered domain drives M-phase supershift and robust activation.
- This comprehensive phosphorylation occurs independently of Cdk1 or other major mitotic kinases.
- A substrate-mediated assembly of phosphorylation machinery enables continuous multisite phosphorylation.
- Site-specific phosphorylation by Cdk1/mitotic kinases causes modest pre-M-phase shifts and activation.
Conclusions:
- Cdc25C regulation during M-phase induction follows a two-stage phosphorylation framework.
- Stage 1: Site-specific phosphorylation by Cdk1/mitotic kinases prior to M-phase onset.
- Stage 2: Site-comprehensive phosphorylation of the regulatory domain at M-phase onset, leading to robust activation.
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