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Mitotic phosphatase activity is required for MCC maintenance during the spindle checkpoint.

Publication ,  Journal Article
Foss, KM; Robeson, AC; Kornbluth, S; Zhang, L
Published in: Cell cycle (Georgetown, Tex.)
January 2016

The spindle checkpoint prevents activation of the anaphase-promoting complex (APC/C) until all chromosomes are correctly attached to the mitotic spindle. Early in mitosis, the mitotic checkpoint complex (MCC) inactivates the APC/C by binding the APC/C activating protein CDC20 until the chromosomes are properly aligned and attached to the mitotic spindle, at which point MCC disassembly releases CDC20 to activate the APC/C. Once the APC/C is activated, it targets cyclin B and securin for degradation, and the cell progresses into anaphase. While phosphorylation is known to drive many of the events during the checkpoint, the precise molecular mechanisms regulating spindle checkpoint maintenance and inactivation are still poorly understood. We sought to determine the role of mitotic phosphatases during the spindle checkpoint. To address this question, we treated spindle checkpoint-arrested cells with various phosphatase inhibitors and examined the effect on the MCC and APC/C activation. Using this approach we found that 2 phosphatase inhibitors, calyculin A and okadaic acid (1 μM), caused MCC dissociation and APC/C activation leading to cyclin A and B degradation in spindle checkpoint-arrested cells. Although the cells were able to degrade cyclin B, they did not exit mitosis as evidenced by high levels of Cdk1 substrate phosphorylation and chromosome condensation. Our results provide the first evidence that phosphatases are essential for maintenance of the MCC during operation of the spindle checkpoint.

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Published In

Cell cycle (Georgetown, Tex.)

DOI

EISSN

1551-4005

ISSN

1538-4101

Publication Date

January 2016

Volume

15

Issue

2

Start / End Page

225 / 233

Related Subject Headings

  • Spindle Apparatus
  • Signal Transduction
  • Securin
  • Proteolysis
  • Proteasome Endopeptidase Complex
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Oxazoles
  • Okadaic Acid
  • Marine Toxins
 

Citation

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MLA
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Foss, K. M., Robeson, A. C., Kornbluth, S., & Zhang, L. (2016). Mitotic phosphatase activity is required for MCC maintenance during the spindle checkpoint. Cell Cycle (Georgetown, Tex.), 15(2), 225–233. https://doi.org/10.1080/15384101.2015.1121331
Foss, Kristen M., Alexander C. Robeson, Sally Kornbluth, and Liguo Zhang. “Mitotic phosphatase activity is required for MCC maintenance during the spindle checkpoint.Cell Cycle (Georgetown, Tex.) 15, no. 2 (January 2016): 225–33. https://doi.org/10.1080/15384101.2015.1121331.
Foss KM, Robeson AC, Kornbluth S, Zhang L. Mitotic phosphatase activity is required for MCC maintenance during the spindle checkpoint. Cell cycle (Georgetown, Tex). 2016 Jan;15(2):225–33.
Foss, Kristen M., et al. “Mitotic phosphatase activity is required for MCC maintenance during the spindle checkpoint.Cell Cycle (Georgetown, Tex.), vol. 15, no. 2, Jan. 2016, pp. 225–33. Epmc, doi:10.1080/15384101.2015.1121331.
Foss KM, Robeson AC, Kornbluth S, Zhang L. Mitotic phosphatase activity is required for MCC maintenance during the spindle checkpoint. Cell cycle (Georgetown, Tex). 2016 Jan;15(2):225–233.

Published In

Cell cycle (Georgetown, Tex.)

DOI

EISSN

1551-4005

ISSN

1538-4101

Publication Date

January 2016

Volume

15

Issue

2

Start / End Page

225 / 233

Related Subject Headings

  • Spindle Apparatus
  • Signal Transduction
  • Securin
  • Proteolysis
  • Proteasome Endopeptidase Complex
  • Phosphorylation
  • Phosphoprotein Phosphatases
  • Oxazoles
  • Okadaic Acid
  • Marine Toxins