Centrosomes and checkpoints: the MPS1 family of kinases

Winey, Mark; Huneycutt, Brenda J.

doi:10.1038/sj.onc.1205712

Cited by 58 publications

(57 citation statements)

References 52 publications

(74 reference statements)

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“…Mps1p protein kinase activity is required for SAC function in yeast and higher eukaryotes [reviewed in Abrieu et al, 2000;Jones et al, 2005;Winey and Huneycutt 2002]. Mps1p phosphorylates Mad1p in vitro and is required for the hyperphosphorylation of Mad1p upon SAC activation [Hardwick and Murray, 1995;Hardwick et al, 1996], but it has not been demonstrated that Mad1p is its direct in vivo substrate.…”

Section: Protein Kinases and Phosphorylation In The Spindle Checkpointmentioning

confidence: 99%

SAC‐ing mitotic errors: How the spindle assembly checkpoint (SAC) plays defense against chromosome mis‐segregation

Kadura

Sazer

2005

Cell Motil. Cytoskeleton

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Section: Protein Kinases and Phosphorylation In The Spindle Checkpointmentioning

confidence: 99%

SAC‐ing mitotic errors: How the spindle assembly checkpoint (SAC) plays defense against chromosome mis‐segregation

Kadura

Sazer

2005

Cell Motil. Cytoskeleton

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“…Defects in centrosome duplication (1,2) or in the spindle checkpoint (3) can disrupt normal progression of mitosis leading to chromosome segregation errors and aneuploidy, a hallmark of human tumors. A handful of protein kinase families, including the Cyclin-dependent kinase (cdk), Polo, Aurora, NIMA, Bub (4), and Mps1 (4,5) families, regulate centrosome duplication and mitotic progression, and thus protect against genetic instability and aneuploidy.…”

mentioning

confidence: 99%

Human Mps1 protein kinase is required for centrosome duplication and normal mitotic progression

Fisk

Mattison

Winey

2003

Proc. Natl. Acad. Sci. U.S.A.

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171

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The mitotic spindle is essential for the maintenance of genetic stability, and in budding yeast its assembly and function depend on the Mps1 protein kinase. Mps1p is required for centrosome duplication and the spindle checkpoint. Several recent reports demonstrate that vertebrate Mps1 proteins regulate the spindle checkpoint, but reports conflict regarding their role in centrosome duplication. Here we provide multiple lines of evidence that the human Mps1 protein (hMps1) is required for centrosome duplication. A recently described rabbit polyclonal antibody against hMps1 specifically recognizes centrosomes in a variety of human cell types. Overexpression of a dominant-negative version of hMps1 (hMps1KD) can prevent centrosome duplication in a variety of cell types, and active hMps1 accelerates centrosome reduplication in U2OS cells. Finally, we demonstrate that disruption of hMps1 function with pools of hMps1-specific small interfering RNAs causes a pleiotropic phenotype resulting from the combination of severe mitotic abnormalities and failures in centrosome duplication. This approach demonstrates that hMps1 is required for centrosome duplication and for the normal progression of mitosis, and suggests that the threshold level of hMps1 function required for centrosome duplication is lower than that required for hMps1 mitotic functions.

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“…TTK/hMps1/PYT is a human homolog of the yeast Mps1 family of protein kinases that are highly expressed in proliferating cells (Mills et al, 1992;Lindberg et al, 1993;Winey and Huneycutt, 2002). It was first discovered through screening expression libraries with antiphosphotyrosine antibodies, and later shown to be a dual specificity protein kinase that phosphorylates tyrosine or serine/threonine residues (Mills et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

The cell cycle checkpoint kinase CHK2 mediates DNA damage-induced stabilization of TTK/hMps1

Huang

Lin

et al. 2009

Oncogene

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Cell cycle progression is monitored constantly to ensure faithful passage of genetic codes and genome stability. We have demonstrated previously that, upon DNA damage, TTK/hMps1 activates the checkpoint kinase CHK2 by phosphorylating CHK2 at Thr68. However, it remains to be determined whether and how TTK/hMps1 responds to DNA damage. In this report, we present evidence that TTK/hMps1 can be induced by DNA damage in normal human fibroblasts. Interestingly, the induction depends on CHK2 because CHK2-targeting small interfering RNA or a CHK2 inhibitor abolishes the increase. Such induction is mediated through phosphorylation of TTK/hMps1 at Thr288 by CHK2 and requires the CHK2 SQ/TQ cluster domain/forkhead-associated domain. In cells, TTK/ hMps1 phosphorylation at Thr288 is induced by DNA damage and forms nuclear foci, which colocalize partially with c-H2AX. Reexpression of TTK/hMps1 T288A mutant in TTK/hMps1-knockdown cells causes a defect in G 2 /M arrest, suggesting that phosphorylation at this site participates in the proper checkpoint execution. Our study uncovered a regulatory loop between TTK/hMps1 and CHK2 whereby DNA damage-activated CHK2 may facilitate the stabilization of TTK/hMps1, therefore maintaining the checkpoint control.

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Centrosomes and checkpoints: the MPS1 family of kinases

Cited by 58 publications

References 52 publications

SAC‐ing mitotic errors: How the spindle assembly checkpoint (SAC) plays defense against chromosome mis‐segregation

SAC‐ing mitotic errors: How the spindle assembly checkpoint (SAC) plays defense against chromosome mis‐segregation

Human Mps1 protein kinase is required for centrosome duplication and normal mitotic progression

The cell cycle checkpoint kinase CHK2 mediates DNA damage-induced stabilization of TTK/hMps1

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