English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C

MPS-Authors
/persons/resource/persons241192

Zhang,  S.
Department of Molecular Biology, MPI for Biophysical Chemistry, Max Planck Society;

Locator
There are no locators available
Fulltext (public)

3164216.pdf
(Publisher version), 6MB

Supplementary Material (public)

3164216_Suppl_1.pdf
(Supplementary material), 30MB

3164216_Suppl_2.pdf
(Supplementary material), 200KB

3164216_Suppl_3.pdf
(Supplementary material), 55KB

3164216_Suppl_4.avi
(Supplementary material), 199KB

3164216_Suppl_5.avi
(Supplementary material), 208KB

3164216_Suppl_6.avi
(Supplementary material), 202KB

3164216_Suppl_7.avi
(Supplementary material), 242KB

3164216_Suppl_8.avi
(Supplementary material), 281KB

Citation

Zhang, S., Tischer, T., & Barford, D. (2019). Cyclin A2 degradation during the spindle assembly checkpoint requires multiple binding modes to the APC/C. Nature Communications, 10: 3863. doi:10.1038/s41467-019-11833-2.


Cite as: http://hdl.handle.net/21.11116/0000-0004-AB15-4
Abstract
The anaphase-promoting complex/cyclosome (APC/C) orchestrates cell cycle progression by controlling the temporal degradation of specific cell cycle regulators. Although cyclin A2 and cyclin B1 are both targeted for degradation by the APC/C, during the spindle assembly checkpoint (SAC), the mitotic checkpoint complex (MCC) represses APC/C's activity towards cyclin B1, but not cyclin A2. Through structural, biochemical and in vivo analysis, we identify a non-canonical D box (D2) that is critical for cyclin A2 ubiquitination in vitro and degradation in vivo. During the SAC, cyclin A2 is ubiquitinated by the repressed APC/C-MCC, mediated by the cooperative engagement of its KEN and D2 boxes, ABBA motif, and the cofactor Cks. Once the SAC is satisfied, cyclin A2 binds APC/C-Cdc20 through two mutually exclusive binding modes, resulting in differential ubiquitination efficiency. Our findings reveal that a single substrate can engage an E3 ligase through multiple binding modes, affecting its degradation timing and efficiency.