Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry

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Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry. / Hein, Jamin B; Nilsson, Jakob.

In: Nature Communications, Vol. 7, 10975, 03.2016.

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

Harvard

Hein, JB & Nilsson, J 2016, 'Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry', Nature Communications, vol. 7, 10975. https://doi.org/10.1038/ncomms10975

APA

Hein, J. B., & Nilsson, J. (2016). Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry. Nature Communications, 7, [10975]. https://doi.org/10.1038/ncomms10975

Vancouver

Hein JB, Nilsson J. Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry. Nature Communications. 2016 Mar;7. 10975. https://doi.org/10.1038/ncomms10975

Author

Hein, Jamin B ; Nilsson, Jakob. / Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry. In: Nature Communications. 2016 ; Vol. 7.

Bibtex

@article{b24ef32f91e44f87b0e50da4dd3fc5d9,
title = "Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry",
abstract = "Proper cell-cycle progression requires tight temporal control of the Anaphase Promoting Complex/Cyclosome (APC/C), a large ubiquitin ligase that is activated by one of two co-activators, Cdh1 or Cdc20. APC/C and Cdc20 are already present during interphase but APC/C-Cdc20 regulation during this window of the cell cycle, if any, is unknown. Here we show that cyclin A2-Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C-Cdc20 activity. Preventing Cdc20 phosphorylation results in pre-mature activation of the APC/C-Cdc20 and several substrates, including cyclin B1 and A2, are destabilized which lengthens G2 and slows mitotic entry. Expressing non-degradable cyclin A2 but not cyclin B1 restores mitotic entry in these cells. We have thus uncovered a novel positive feedback loop centred on cyclin A2-Cdk2 inhibition of interphase APC/C-Cdc20 to allow further cyclin A2 accumulation and mitotic entry.",
author = "Hein, {Jamin B} and Jakob Nilsson",
year = "2016",
month = mar,
doi = "10.1038/ncomms10975",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Interphase APC/C-Cdc20 inhibition by cyclin A2-Cdk2 ensures efficient mitotic entry

AU - Hein, Jamin B

AU - Nilsson, Jakob

PY - 2016/3

Y1 - 2016/3

N2 - Proper cell-cycle progression requires tight temporal control of the Anaphase Promoting Complex/Cyclosome (APC/C), a large ubiquitin ligase that is activated by one of two co-activators, Cdh1 or Cdc20. APC/C and Cdc20 are already present during interphase but APC/C-Cdc20 regulation during this window of the cell cycle, if any, is unknown. Here we show that cyclin A2-Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C-Cdc20 activity. Preventing Cdc20 phosphorylation results in pre-mature activation of the APC/C-Cdc20 and several substrates, including cyclin B1 and A2, are destabilized which lengthens G2 and slows mitotic entry. Expressing non-degradable cyclin A2 but not cyclin B1 restores mitotic entry in these cells. We have thus uncovered a novel positive feedback loop centred on cyclin A2-Cdk2 inhibition of interphase APC/C-Cdc20 to allow further cyclin A2 accumulation and mitotic entry.

AB - Proper cell-cycle progression requires tight temporal control of the Anaphase Promoting Complex/Cyclosome (APC/C), a large ubiquitin ligase that is activated by one of two co-activators, Cdh1 or Cdc20. APC/C and Cdc20 are already present during interphase but APC/C-Cdc20 regulation during this window of the cell cycle, if any, is unknown. Here we show that cyclin A2-Cdk2 binds and phosphorylates Cdc20 in interphase and this inhibits APC/C-Cdc20 activity. Preventing Cdc20 phosphorylation results in pre-mature activation of the APC/C-Cdc20 and several substrates, including cyclin B1 and A2, are destabilized which lengthens G2 and slows mitotic entry. Expressing non-degradable cyclin A2 but not cyclin B1 restores mitotic entry in these cells. We have thus uncovered a novel positive feedback loop centred on cyclin A2-Cdk2 inhibition of interphase APC/C-Cdc20 to allow further cyclin A2 accumulation and mitotic entry.

U2 - 10.1038/ncomms10975

DO - 10.1038/ncomms10975

M3 - Journal article

C2 - 26960431

VL - 7

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 10975

ER -

ID: 160132591