Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex

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Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex. / Sedgwick, G.G.; Hayward, D.G.; Nilsson, J.; Di Fiore, B.; Pines, J.; Pardo, Mercedes; Yu, L.

In: E M B O Journal, Vol. 32, No. 2, 23.01.2013, p. 303-314.

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

Harvard

Sedgwick, GG, Hayward, DG, Nilsson, J, Di Fiore, B, Pines, J, Pardo, M & Yu, L 2013, 'Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex', E M B O Journal, vol. 32, no. 2, pp. 303-314. https://doi.org/10.1038/emboj.2012.335

APA

Sedgwick, G. G., Hayward, D. G., Nilsson, J., Di Fiore, B., Pines, J., Pardo, M., & Yu, L. (2013). Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex. E M B O Journal, 32(2), 303-314. https://doi.org/10.1038/emboj.2012.335

Vancouver

Sedgwick GG, Hayward DG, Nilsson J, Di Fiore B, Pines J, Pardo M et al. Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex. E M B O Journal. 2013 Jan 23;32(2):303-314. https://doi.org/10.1038/emboj.2012.335

Author

Sedgwick, G.G. ; Hayward, D.G. ; Nilsson, J. ; Di Fiore, B. ; Pines, J. ; Pardo, Mercedes ; Yu, L. / Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex. In: E M B O Journal. 2013 ; Vol. 32, No. 2. pp. 303-314.

Bibtex

@article{195424b3e8084164b9c4fbe7d3152edc,
title = "Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex",
abstract = "The Anaphase Promoting Complex/Cyclosome (APC/C) in complex with its co-activator Cdc20 is responsible for targeting proteins for ubiquitin-mediated degradation during mitosis. The activity of APC/C-Cdc20 is inhibited during prometaphase by the Spindle Assembly Checkpoint (SAC) yet certain substrates escape this inhibition. Nek2A degradation during prometaphase depends on direct binding of Nek2A to the APC/C via a C-terminal MR dipeptide but whether this motif alone is sufficient is not clear. Here, we identify Kif18A as a novel APC/C-Cdc20 substrate and show that Kif18A degradation depends on a C-terminal LR motif. However in contrast to Nek2A, Kif18A is not degraded until anaphase showing that additional mechanisms contribute to Nek2A degradation. We find that dimerization via the leucine zipper, in combination with the MR motif, is required for stable Nek2A binding to and ubiquitination by the APC/C. Nek2A and the mitotic checkpoint complex (MCC) have an overlap in APC/C subunit requirements for binding and we propose that Nek2A binds with high affinity to apo-APC/C and is degraded by the pool of Cdc20 that avoids inhibition by the SAC.",
author = "G.G. Sedgwick and D.G. Hayward and J. Nilsson and {Di Fiore}, B. and J. Pines and Mercedes Pardo and L. Yu",
year = "2013",
month = jan,
day = "23",
doi = "10.1038/emboj.2012.335",
language = "English",
volume = "32",
pages = "303--314",
journal = "E M B O Journal",
issn = "0261-4189",
publisher = "Wiley-Blackwell",
number = "2",

}

RIS

TY - JOUR

T1 - Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex

AU - Sedgwick, G.G.

AU - Hayward, D.G.

AU - Nilsson, J.

AU - Di Fiore, B.

AU - Pines, J.

AU - Pardo, Mercedes

AU - Yu, L.

PY - 2013/1/23

Y1 - 2013/1/23

N2 - The Anaphase Promoting Complex/Cyclosome (APC/C) in complex with its co-activator Cdc20 is responsible for targeting proteins for ubiquitin-mediated degradation during mitosis. The activity of APC/C-Cdc20 is inhibited during prometaphase by the Spindle Assembly Checkpoint (SAC) yet certain substrates escape this inhibition. Nek2A degradation during prometaphase depends on direct binding of Nek2A to the APC/C via a C-terminal MR dipeptide but whether this motif alone is sufficient is not clear. Here, we identify Kif18A as a novel APC/C-Cdc20 substrate and show that Kif18A degradation depends on a C-terminal LR motif. However in contrast to Nek2A, Kif18A is not degraded until anaphase showing that additional mechanisms contribute to Nek2A degradation. We find that dimerization via the leucine zipper, in combination with the MR motif, is required for stable Nek2A binding to and ubiquitination by the APC/C. Nek2A and the mitotic checkpoint complex (MCC) have an overlap in APC/C subunit requirements for binding and we propose that Nek2A binds with high affinity to apo-APC/C and is degraded by the pool of Cdc20 that avoids inhibition by the SAC.

AB - The Anaphase Promoting Complex/Cyclosome (APC/C) in complex with its co-activator Cdc20 is responsible for targeting proteins for ubiquitin-mediated degradation during mitosis. The activity of APC/C-Cdc20 is inhibited during prometaphase by the Spindle Assembly Checkpoint (SAC) yet certain substrates escape this inhibition. Nek2A degradation during prometaphase depends on direct binding of Nek2A to the APC/C via a C-terminal MR dipeptide but whether this motif alone is sufficient is not clear. Here, we identify Kif18A as a novel APC/C-Cdc20 substrate and show that Kif18A degradation depends on a C-terminal LR motif. However in contrast to Nek2A, Kif18A is not degraded until anaphase showing that additional mechanisms contribute to Nek2A degradation. We find that dimerization via the leucine zipper, in combination with the MR motif, is required for stable Nek2A binding to and ubiquitination by the APC/C. Nek2A and the mitotic checkpoint complex (MCC) have an overlap in APC/C subunit requirements for binding and we propose that Nek2A binds with high affinity to apo-APC/C and is degraded by the pool of Cdc20 that avoids inhibition by the SAC.

UR - http://www.scopus.com/inward/record.url?scp=84872849589&partnerID=8YFLogxK

U2 - 10.1038/emboj.2012.335

DO - 10.1038/emboj.2012.335

M3 - Journal article

C2 - 23288039

AN - SCOPUS:84872849589

VL - 32

SP - 303

EP - 314

JO - E M B O Journal

JF - E M B O Journal

SN - 0261-4189

IS - 2

ER -

ID: 46439039