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Updated: May 11, 2026

Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange
Published on: April 27, 2017
The mouse Mps1p-like kinase regulates centrosome duplication
Abstract:
The yeast Mps1p protein kinase acts in centrosome duplication and the spindle assembly checkpoint. We demonstrate here that a mouse Mps1p ortholog (esk, which we designate mMps1p) regulates centrosome duplication. Endogenous mMps1p and overexpressed GFP-mMps1p localize to centrosomes and kinetochores in mouse cells. Overexpression of GFP-mMps1p causes reduplication of centrosomes during S phase arrest. In contrast, a kinase-deficient mutant blocks centrosome duplication altogether. Control of centrosome duplication by mMps1p requires a known regulator of the process, Cdk2. Inhibition of Cdk2 prevents centrosome reduplication and destabilizes mMps1p, causing its subsequent loss from centrosomes, suggesting that Cdk2 promotes mMps1p's centrosome duplication function by regulating its stability during S phase. Thus, mMps1p, an in vitro Cdk2 substrate, regulates centrosome duplication jointly with Cdk2.
Insights
Mouse Mps1p (mMps1p) protein kinase controls centrosome duplication, working with Cdk2. mMps1p stability, regulated by Cdk2, is crucial for this process during S phase.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Background:
- The yeast Mps1p protein kinase is essential for centrosome duplication and the spindle assembly checkpoint.
- Understanding the function of Mps1p orthologs in mammalian cells is crucial for comprehending cell cycle regulation.
Purpose of the Study:
- To investigate the role of the mouse Mps1p ortholog (mMps1p) in centrosome duplication.
- To elucidate the regulatory relationship between mMps1p and Cdk2 in controlling centrosome duplication.
Main Methods:
- Localization studies of endogenous and overexpressed mMps1p in mouse cells using immunofluorescence.
- Analysis of centrosome duplication in response to mMps1p overexpression and kinase-deficient mMps1p mutants.
- Investigating the effect of Cdk2 inhibition on mMps1p localization and centrosome duplication.
Main Results:
- Endogenous and overexpressed mMps1p localize to centrosomes and kinetochores in mouse cells.
- Overexpression of mMps1p leads to centrosome reduplication during S phase arrest, while a kinase-deficient mutant inhibits duplication.
- Cdk2 is required for mMps1p-mediated centrosome reduplication, and Cdk2 inhibition destabilizes mMps1p at centrosomes.
Conclusions:
- Mouse Mps1p (mMps1p) is a key regulator of centrosome duplication in mammalian cells.
- Cdk2 regulates mMps1p stability during S phase, thereby controlling its function in centrosome duplication.
- mMps1p functions in concert with Cdk2 to ensure proper centrosome duplication.
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