Coupling of Cdc20 inhibition and activation by BubR1

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Coupling of Cdc20 inhibition and activation by BubR1. / Hein, Jamin B; Garvanska, Dimitriya H; Nasa, Isha; Kettenbach, Arminja N; Nilsson, Jakob.

In: Journal of Cell Biology, Vol. 220, No. 5, e202012081, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hein, JB, Garvanska, DH, Nasa, I, Kettenbach, AN & Nilsson, J 2021, 'Coupling of Cdc20 inhibition and activation by BubR1', Journal of Cell Biology, vol. 220, no. 5, e202012081. https://doi.org/10.1083/jcb.202012081

APA

Hein, J. B., Garvanska, D. H., Nasa, I., Kettenbach, A. N., & Nilsson, J. (2021). Coupling of Cdc20 inhibition and activation by BubR1. Journal of Cell Biology, 220(5), [e202012081]. https://doi.org/10.1083/jcb.202012081

Vancouver

Hein JB, Garvanska DH, Nasa I, Kettenbach AN, Nilsson J. Coupling of Cdc20 inhibition and activation by BubR1. Journal of Cell Biology. 2021;220(5). e202012081. https://doi.org/10.1083/jcb.202012081

Author

Hein, Jamin B ; Garvanska, Dimitriya H ; Nasa, Isha ; Kettenbach, Arminja N ; Nilsson, Jakob. / Coupling of Cdc20 inhibition and activation by BubR1. In: Journal of Cell Biology. 2021 ; Vol. 220, No. 5.

Bibtex

@article{88a5db305a334504a35d78e9215c2111,
title = "Coupling of Cdc20 inhibition and activation by BubR1",
abstract = "Tight regulation of the APC/C-Cdc20 ubiquitin ligase that targets cyclin B1 for degradation is important for mitotic fidelity. The spindle assembly checkpoint (SAC) inhibits Cdc20 through the mitotic checkpoint complex (MCC). In addition, phosphorylation of Cdc20 by cyclin B1-Cdk1 independently inhibits APC/C-Cdc20 activation. This creates a conundrum for how Cdc20 is activated before cyclin B1 degradation. Here, we show that the MCC component BubR1 harbors both Cdc20 inhibition and activation activities, allowing for cross-talk between the two Cdc20 inhibition pathways. Specifically, BubR1 acts as a substrate specifier for PP2A-B56 to enable efficient Cdc20 dephosphorylation in the MCC. A mutant Cdc20 mimicking the dephosphorylated state escapes a mitotic checkpoint arrest, arguing that restricting Cdc20 dephosphorylation to the MCC is important. Collectively, our work reveals how Cdc20 can be dephosphorylated in the presence of cyclin B1-Cdk1 activity without causing premature anaphase onset.",
author = "Hein, {Jamin B} and Garvanska, {Dimitriya H} and Isha Nasa and Kettenbach, {Arminja N} and Jakob Nilsson",
year = "2021",
doi = "10.1083/jcb.202012081",
language = "English",
volume = "220",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "5",

}

RIS

TY - JOUR

T1 - Coupling of Cdc20 inhibition and activation by BubR1

AU - Hein, Jamin B

AU - Garvanska, Dimitriya H

AU - Nasa, Isha

AU - Kettenbach, Arminja N

AU - Nilsson, Jakob

PY - 2021

Y1 - 2021

N2 - Tight regulation of the APC/C-Cdc20 ubiquitin ligase that targets cyclin B1 for degradation is important for mitotic fidelity. The spindle assembly checkpoint (SAC) inhibits Cdc20 through the mitotic checkpoint complex (MCC). In addition, phosphorylation of Cdc20 by cyclin B1-Cdk1 independently inhibits APC/C-Cdc20 activation. This creates a conundrum for how Cdc20 is activated before cyclin B1 degradation. Here, we show that the MCC component BubR1 harbors both Cdc20 inhibition and activation activities, allowing for cross-talk between the two Cdc20 inhibition pathways. Specifically, BubR1 acts as a substrate specifier for PP2A-B56 to enable efficient Cdc20 dephosphorylation in the MCC. A mutant Cdc20 mimicking the dephosphorylated state escapes a mitotic checkpoint arrest, arguing that restricting Cdc20 dephosphorylation to the MCC is important. Collectively, our work reveals how Cdc20 can be dephosphorylated in the presence of cyclin B1-Cdk1 activity without causing premature anaphase onset.

AB - Tight regulation of the APC/C-Cdc20 ubiquitin ligase that targets cyclin B1 for degradation is important for mitotic fidelity. The spindle assembly checkpoint (SAC) inhibits Cdc20 through the mitotic checkpoint complex (MCC). In addition, phosphorylation of Cdc20 by cyclin B1-Cdk1 independently inhibits APC/C-Cdc20 activation. This creates a conundrum for how Cdc20 is activated before cyclin B1 degradation. Here, we show that the MCC component BubR1 harbors both Cdc20 inhibition and activation activities, allowing for cross-talk between the two Cdc20 inhibition pathways. Specifically, BubR1 acts as a substrate specifier for PP2A-B56 to enable efficient Cdc20 dephosphorylation in the MCC. A mutant Cdc20 mimicking the dephosphorylated state escapes a mitotic checkpoint arrest, arguing that restricting Cdc20 dephosphorylation to the MCC is important. Collectively, our work reveals how Cdc20 can be dephosphorylated in the presence of cyclin B1-Cdk1 activity without causing premature anaphase onset.

U2 - 10.1083/jcb.202012081

DO - 10.1083/jcb.202012081

M3 - Journal article

C2 - 33819340

VL - 220

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 5

M1 - e202012081

ER -

ID: 259834392